Abstract
An efficient method for the synthesis of 2-(o-monofluoroalkenylaryl)quinazolinone derivatives was developed. In this context, the quinazolinone ring served as the inherent directing group, 2,2-difluorovinyl tosylate was used as the monofluoroolefin synthon, and Rh(III)-catalyzed C–H bond difluorovinylation of 2-arylquinazolinons was performed to give the corresponding monofluoroalkene-containing quinazolinons in yields of 65–92%. The method is characterized by broad synthetic utility, mild conditions, and high efficiency.
Introduction
In recent decades, organofluorine chemistry has been widely developed in the fields of medicine and pesticides.1 The combination of a fluorine atom or a fluorine-containing compound with a small organic molecule increases the organic molecule’s polarity and lipophilicity and alters its biological activity and physicochemical properties.2 Among fluorine-containing compounds, monofluoroolefins play an important role in organic synthesis, medicinal chemistry, and peptide chemistry.3 Consequently, a growing number of efficient methodologies for the synthesis of monofluoroalkenes have been reported.4
In recent years, transition-metal-catalyzed C–H bond activations have been implemented in order to introduce a monofluoroolefin moiety into small organic molecules.5 Various fluorine-containing reagents, such as gem-difluoroalkenes,5a−5ia-fluoroacrylic acids,5j and gem-bromofluoroalkenes,5k have been employed as monofluoroolefin synthons. Among these reagents, 2,2-difluorovinyl tosylate has seen broad use in recent years (Scheme 1).6 For example, Li and Wang reported the use of 2,2-difluorovinyl tosylate as a coupling reagent in the Rh(III)-catalyzed C–H activation of the N–X bond of benzamides. This allowed for the assembly of a monofluorinated alkene intermediate with retention of the tosylate functionality, allowing for the preparation of the corresponding fluorinated heterocycles under various conditions (Scheme 1a,b).6a,6b Li described the Rh(III)-catalyzed α-fluoroalkenylation of N-nitrosoanilines with 2,2-difluorovinyl tosylates via C–H bond activation and subsequent β-F elimination to form the desired monofluoroalkene-containing compounds (Scheme 1c).6c
Scheme 1. (a–d) α-Fluoroalkenylation Using Difluoroalkene Tosylates.
The quinazolinone skeleton is present in numerous natural products7 and has a wide range of applications in medicine and biology.8 So far, tremendous efforts have been devoted to the development of new synthetic methods for the construction of diverse quinazolinone architectures and the evaluation of their bioactivities.9,10 In the past few years, our group has focused extensively on the development of methods for the synthesis of quinazolinone cores and the late-stage functionalization of 2-arylquinazolinones with a desire to construct a quinazolinone-based molecular library for bioactivity assays.11 Despite progress, there is room for improvement with regard to efficiency and selectivity, especially for the introduction of a monofluoroalkene moiety into the quinazolinone skeleton to form novel monofluoroalkene-quinazolinone derivatives. Monofluoroolefins and the quinazolinone core are important structural motifs in pharmaceuticals and biologically active molecules. Monofluoroolefin-containing quinazolinones may exhibit a wide range of potent applications in the pharmaceutical, agrochemical, and material sciences. Thus, the development of efficient and straightforward protocols to access monofluoroolefin-containing quinazolinones is highly desirable. Thus, we have focused on the preparation of a diverse range of monofluoroolefin-containing quinazolinones (Scheme 1d).
Results and Discussion
We initiated our investigation by screening the coupling reaction conditions between 2-(p-methylphenyl)quinazolinone 1a (0.2 mmol) with 2,2-difluorovinyl tosylate 2a (1.1 equiv) in the presence of RhCp*(MeCN)3(SbF6)2 (4.0 mol %) and CsOPiv (1.0 equiv). Fortunately, the corresponding monofluoroolefin-quinazolinone compound 3a was isolated in a yield of 39% when the reaction was conducted in CF3CH2OH at 60 °C (entry 1). The structure of 3a was confirmed unambiguously by X-ray crystal diffraction (see the Supporting Information). The results of solvent screening indicated that carrying out the reaction in HFIP gave the corresponding product in a high yield of 86% (entries 2–11). The fluorinated solvent HFIP not only have acidic properties but also have H-bonding with the substrate, which can enhance the reaction.12 Next, the additives, such as Cs2CO3, CsOAc, CsF, and so forth were examined, and no better result was obtained (entries 12–14). Lower yields were obtained when other catalysts such as IrCp*Cl2/AgSbF6 or RhCp*Cl2/AgSbF6 were used (entries 15–16). The desired product was obtained in 92% yield when the reaction time was reduced to 6 h (entry 17). Increasing or decreasing the reaction temperature resulted in slightly diminished yields (entries 18–19). Decreasing the loading of CsOPiv gave lower product yields (entries 20–21). Control experiments showed that none of the desired product was obtained in the absence of the RhCp*(MeCN)3(SbF6)2 catalyst (entry 22) (Table 1).
Table 1. Optimization of the Reaction Conditionsa.
| entry | catalyst (5 mol %) | solvent | additive | T (°C) | yield (%) |
|---|---|---|---|---|---|
| 1 | RhCp*(MeCN)3(SbF6)2 | CF3CH2OH | CsOPiv | 60 | 39 |
| 2 | RhCp*(MeCN)3(SbF6)2 | MeOH | CsOPiv | 60 | 22 |
| 3 | RhCp*(MeCN)3(SbF6)2 | EtOH | CsOPiv | 60 | 19 |
| 4 | RhCp*(MeCN)3(SbF6)2 | 1,4-dioxane | CsOPiv | 60 | trace |
| 5 | RhCp*(MeCN)3(SbF6)2 | DMF | CsOPiv | 60 | NR |
| 6 | RhCp*(MeCN)3(SbF6)2 | DMSO | CsOPiv | 60 | NR |
| 7 | RhCp*(MeCN)3(SbF6)2 | THF | CsOPiv | 60 | trace |
| 8 | RhCp*(MeCN)3(SbF6)2 | toluene | CsOPiv | 60 | NR |
| 9 | RhCp*(MeCN)3(SbF6)2 | benzotrifluoride | CsOPiv | 60 | NR |
| 10 | RhCp*(MeCN)3(SbF6)2 | t-BuOH | CsOPiv | 60 | NR |
| 11 | RhCp*(MeCN)3(SbF6)2 | HFIP | CsOPiv | 60 | 86 |
| 12 | RhCp*(MeCN)3(SbF6)2 | HFIP | CsOAc | 60 | 76 |
| 13 | RhCp*(MeCN)3(SbF6)2 | HFIP | Cs2CO3 | 60 | 80 |
| 14 | RhCp*(MeCN)3(SbF6)2 | HFIP | CsF | 60 | 41 |
| 15 | IrCp*Cl2/AgSbF6 | HFIP | CsOPiv | 60 | 22 |
| 16 | RhCp*Cl2/AgSbF6 | HFIP | CsOPiv | 60 | 70 |
| 17b | RhCp*(MeCN)3(SbF6)2 | HFIP | CsOPiv | 60 | 92 |
| 18b | RhCp*(MeCN)3(SbF6)2 | HFIP | CsOPiv | 80 | 82 |
| 19b | RhCp*(MeCN)3(SbF6)2 | HFIP | CsOPiv | 40 | 72 |
| 20b,c | RhCp*(MeCN)3(SbF6)2 | HFIP | CsOPiv | 60 | 77 |
| 21b | RhCp*(MeCN)3(SbF6)2 | HFIP | 60 | 74 | |
| 22b | HFIP | CsOPiv | 60 | NR |
Yields based on isolated.
Time was 6 h.
CsOpiv was added 0.5 equiv.
After establishing the optimized conditions, we investigated the generality and the substrate scope of the reaction. The results are presented in Table 2. As shown in Table 2, a number of substrates bearing different substituents were amenable to the reaction conditions, giving the corresponding products in good to excellent yields under the optimal conditions. First, the effects of R1 on the reaction were explored. The results revealed that the electronic nature and the position of the R1 substituent have a significant influence on the reaction. When the substituent R1 is at the para position of the 2-arylquinazolinone and is an electron-donating group, such as methyl, ethyl, i-propyl, methoxy, ethoxy, or an N,N-dimethylamino substituent, the desired products are obtained in excellent yields of 83–92% (entries 3a–3f). When R1 is at the para position or ortho position of the 2-aryl group and is electron-withdrawing in character (F, Cl, Br, CN, or NO2), no reaction occurs (3h–3i). When the substituent R1 is at the ortho position and is an electron-donating group, such as a methyl, methoxy, or ethoxy substituent, the expected products are prepared in good to excellent yields (3j–3l). Substrates with an electron-donating R1 group at the meta position of the 2-aryl functionality (methyl, methoxy, and ethoxy) were not amenable to the reaction conditions (3m–3n). However, the desired products were obtained in good yields when an electron-withdrawing R1 group is present at this position (3o–3p).
Table 2. Scope Investigation for the Reaction of 2-Arylquinazolinones 1 and 2,2-Difluorovinyl Tosylate 2a.
Yields based on isolated. Reaction conditions: 1 (0.2 mol), 2 (0.22 mol), RhCp*(MeCN)3(SbF6)2 (5.0 mol %), CsOPiv (1.0 equiv), HFIP (1.5 mL), 60 °C, 6 h, under air. NR = no reaction.
Subsequently, the effects of the R2 group on the quinazolinone ring were explored. Surprisingly, electron-withdrawing and electron-donating groups are tolerated, providing the desired products in excellent yields, no matter what the position of the R2 substituent is (entries 3q–3za).
To demonstrate the potential synthetic utility of this reaction, we performed a gram–scale reaction with 2-p-methylphenyl-quinazolinone. As shown in Scheme 2, the product (3a) was isolated in a yield of 84%.
Scheme 2. Gram-Scale Reaction.
On the basis of previous reports,6 a plausible mechanism is described in Scheme 3. First, an active cation Rh(III) reacts with 2-arylquinazolinone 1 via a key C–H activation to generate the five-membered rhodacycle intermediate A, which coordinates with the difluoroolefin to give intermediate B. Next, insertion of the difluoroolefin into the C–Rh bond produces a seven-membered Rh(III) complex C, which undergoes selective β-F elimination via the syn-coplanar state to form the product 3a and Rh(III).
Scheme 3. Plausible Mechanism for the Reaction of 2-Arylquinazolinones and 2,2-Difluorovinyl Tosylate.
Conclusions
In summary, We have developed an efficient method for the synthesis of 2-(o-monofluoroalkenylaryl)quinazolinone derivatives. The reaction of 2-arylquinazolinones and 2,2-difluorovinyl tosylate in the presence of a Rh catalyst produces the corresponding products via C–H bond activation and C–F bond cleavage. The methodology is available to a wide range of substrates, and the presence of a double bond provides the possibility for subsequent research.
Experimental Section
Unless otherwise noted, all reactions were carried out under air atmosphere unless otherwise stated. Commercial reagents were purchased from Aldrich, Alfa, or other commercial suppliers. Commercial reagents were used without further purification. Reactions were conducted using standard techniques on the vacuum line. Analytical thin-layer chromatography (TLC) was performed using glass plates precoated with 0.25 mm 230–400 mesh silica gel impregnated with a fluorescent indicator (254 nm). Flash column chromatography was performed using silica gel (60 °A pore size, 32–63 μm, standard grade). Organic solutions were concentrated on rotary evaporators at 20 Torr (house vacuum) at 25–35 °C. The 1H NMR spectra were recorded on a 400 MHz NMR spectrometer. The 13C NMR spectra were recorded at 100 MHz. The 19F NMR spectra were recorded at 375 MHz. Nuclear magnetic resonance (NMR) spectra are recorded in parts per million (ppm) from internal standard tetramethylsilane (TMS) on the δ scale.
General Procedures for Synthesis of Compound 3
A mixture of 2-arylquinazolinone 1 (0.2 mmol), 2,2-difluorovinyl tosylate 2 (56.16 mg, 0.24 mmol), RhCp*(MeCN)3(SbF6)2 (8.33 mg, 5 mol %), and CsOPiv (46.80 mg, 0.2 mmol) in HFIP (1.5 mL) was stirred at 60 °C until 1a was completed consumed (detected by TLC). Evaporation of the solvent followed purification by column chromatograph over silica gel (normal ratio: petroleum ether/ethyl acetate = 3/1) provided the corresponding product 3.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-p-methylphenyl]-3H-quinazolin-4-one (3a)
The product is obtained as a white solid in 92% yield, 83 mg, mp 205–208 °C, Rf = 0.45 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.56 (s, 1H), 8.17 (d J = 7.2 Hz, 1H), 7.83 (ddd J = 8.4, 7.2, 1.2 Hz, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.59–7.53 (m, 2H), 7.48 (d, J = 8.0 Hz, 1H), 7.46–7.38 (m, 4H), 6.91 (d, J = 20 Hz, 1H), 2.40 (s, 6H). 13C NMR (100 MHz, DMSO-d6): δ 162.1, 153.6, 151.1 (d, 1JC–F = 253.0 Hz), 148.9, 146.5, 140.8, 134.9, 131.7, 131.3, 130.8, 130.5, 129.6 (d, 3JC–F = 4.0 Hz), 128.2, 127.8, 127.4 (d, 2JC–F = 22.0 Hz), 127.3, 126.3, 121.5, 121.2 (d, 2JC–F = 13.0 Hz) 121.1, 21.7, 21.1. 19F NMR (376 MHz, DMSO): δ −117.80. HRMS (ESI) m/z: [M + H]+ calcd for C24H20FN2O4S+ [M + H]+, 451.1122; found, 451.1117.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-p-ethylphenyl]-3H-quinazolin-4-one (3b)
The product is obtained as a white solid in 88% yield, 82 mg, mp 166–168 °C, Rf = 0.46 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.54 (s, 1H), 8.18 (d, J = 7.8 Hz, 1H), 7.83 (t, J = 7.6 Hz, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.59–7.54 (m, 2H), 7.49–7.45 (m, 2H), 7.40 (d, J = 8.4 Hz, 2H), 6.94 (d, J = 20.0 Hz, 1H), 2.70 (q, J = 7.6 Hz, 2H), 2.40 (s, 3H), 1.22 (t, J = 7.6 Hz, 3H). 13C NMR (101 MHz, DMSO-d6): δ 162.1, 153.6, 151.2 (d, 1JC–F = 253.1 Hz), 148.9, 146.9, 146.4, 134.9, 131.7, 130.8, 130.7, 130.6, 130.2, 128.6 (d, 3JC–F = 4.2 Hz), 128.2 127.8, 127.6 (d, 2JC–F = 21.5 Hz), 127.3, 126.3, 121.5, 121.2 (d, 2JC–F = 12.5 Hz), 28.3, 21.63, 15.73. 19F NMR (376 MHz, DMSO-d6): δ −117.59. HRMS (ESI) m/z: [M + H]+ calcd for C25H22FN2O4S+ [M + H]+, 465.1279; found, 465.1286.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-p-i-propylphenyl]-3H-quinazolin-4-one (3c)
The product is obtained as a white solid in 87% yield, 83 mg,, mp 181–183 °C, Rf = 0.45 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.52 (s, 1H), 8.17 (d, J = 7.6 Hz, 1H), 7.83 (t, J = 8.0 Hz, 1H), 7.76 (d, J = 8.0 Hz, 2H), 7.60 (d, J = 8.0 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H), 7.51–7.45 (m, 3H), 7.40 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 20.0 Hz, 1H), 3.00 (m, J = 6.8 Hz, 1H), 2.40 (s, 3H), 1.25 (d, J = 6.8 Hz, 6H). 13C NMR (100 MHz, DMSO-d6): δ 162.0, 153.6, 151.4, 151.2 (d, 1JC–F = 254.0 Hz), 148.9, 146.4, 134. 9, 131.7, 131.1, 130.7, 130.6, 128.7, 128.2, 127.8, 127.6 (d, 2JC–F = 22.0 Hz), 127.3 (d, 3JC–F = 4.0 Hz), 126.3, 121.5, 121.3 (d, 2JC–F = 13.0 Hz), 33.7, 23.9, 21.7. 19F NMR (376 MHz, DMSO-d6): δ −117.35. HRMS (ESI) m/z: [M + H]+ calcd for C26H24FN2O4S+ [M + H]+, 479.1435; found, 479.1449.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-p-methyloxylphenyl]-3H-quinazolin-4-one (3d)
The product is obtained as a white solid in 84% yield, 81 mg,, mp 165–168 °C, Rf = 0.40 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.52 (s, 1H), 8.17 (d, J = 8.0 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.63 (d, J = 8.8 Hz, 1H), 7.54 (t, J = 7.6 Hz, 1H), 7.45 (d, J = 7.6 Hz, 1H), 7.42 (d, J = 8.0 Hz, 2H), 7.17 (dd, J = 8.8, 2.4 Hz, 1H), 7.12 (s, 1H), 7.00 (d, J = 19.6 Hz, 1H), 3.87 (s, 3H), 2.40 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 162.2, 160.7, 153.4, 150.9 (d, 1JC–F = 254.0 Hz), 149.0, 146.5, 134.8, 132.3, 131.7, 130.8, 129.2 (d, 2JC–F = 22.0 Hz), 128.3, 127.7, 127.1, 126.2, 125.6, 121.6 (d, 2JC–F = 12.0 Hz), 121.4, 116.1, 114.8 (d, 3JC–F = 4.0 Hz), 56.2, 21.6. 19F NMR (376 MHz, DMSO-d6): δ −117.57. HRMS (ESI) m/z: [M + H]+ calcd for C24H20FN2O5S+ [M + H]+, 467.1072; found, 467.1077.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-p-ethyloxylphenyl]-3H-quinazolin-4-one (3e)
The product is obtained as a white solid in 83% yield, 77 mg,, mp 178–180 °C, Rf = 0.40 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.50 (s, 1H), 8.17 (d, J = 7.6 Hz, 1H), 7.82 (d, J = 7.2 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 1H), 7.54 (t, J = 7.6 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.41 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.4 Hz, 1H), 7.10 (s, 1H), 7.00 (d, J = 19.6 Hz, 1H), 4.15 (q, J = 6.8 Hz, 2H), 2.40 (s, 3H), 1.36 (t, J = 6.8 Hz, 3H). 13C NMR (101 MHz, DMSO-d6): δ 162.2, 160.0, 153.4, 150.9 (d, 1JC–F = 253.0 Hz), 149.0, 146.4, 134.8, 132.3, 131.7, 130.8, 129.2 (d, 2JC–F = 22.0 Hz), 128.3, 127.7, 127.1, 126.2, 125.5, 121.5 (d, 2JC–F = 12.0 Hz), 121.4, 116.4, 115.2 (d, 3JC–F = 5.0 Hz), 64.2, 21.6, 14.9. 19F NMR (376 MHz, DMSO-d6): δ −117.60. HRMS (ESI) m/z: [M + H]+ calcd for C25H22FN2O5S+ [M + H]+, 481.1228; found, 481.1223.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-p-N,N-dimethylaminophenyl]-3H-quinazolin-4-one (3f)
The product is obtained as a white solid in 83% yield, 80 mg,, mp 199–201 °C, Rf = 0.44 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.34 (s, 1H), 8.12 (d, J = 8.0 Hz, 1H), 7.82 (J = 7.6 Hz, 2H), 7.77 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H), 7.53 (J = 8.4 Hz, 1H), 7.49 (t, J = 8.0 Hz, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.0 Hz, 1H), 6.91 (d, J = 19.6 Hz, 1H), 6.84 (dd, J = 8.8, 2.4 Hz, 1H), 6.70 (s, 1H), 3.00 (s, 6H), 2.40 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 162.5, 153.6, 152.4 (d, 1JC–F = 254.0 Hz), 151.4, 149.2, 146.4, 134.7, 131.8, 131.6, 130.7, 128.8 (d, 2JC–F = 21.0 Hz), 128.3, 127.5, 126.7, 126.2, 121.1, 120.7 (d, 2JC–F = 12.0 Hz), 119.9, 113.1, 112.8 (d, 3JC–F = 4.0 Hz), 40.2, 21.6. 19F NMR (376 MHz, DMSO-d6): δ −114.81. HRMS (ESI) m/z: [M + H]+ calcd for C25H23FN3O4S+ [M + H]+, 480.1388; found, 480.1398.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-phenyl]-3H-quinazolin-4-one (3g)
The product is obtained as a white solid in 83% yield, 73 mg,, mp 188–190 °C, Rf = 0.48 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.62 (s, 1H), 8.21 (d, J = 7.6 Hz, 1H), 7.86 (t, J = 7.6 Hz, 1H), 7.76 (d, J = 8.0 Hz, 2H), 7.78–7.51 (m, 6H), 7.41 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 19.6 Hz, 1H), 2.41 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 162.0, 153.6, 150.9 (d, 1JC–F = 253.0 Hz), 148.9, 146.5, 134.9, 133.3, 131.64, 130.9, 130.9, 130.8, 130.6, 129.2 (d, 3JC–F = 4.0 Hz), 128.2, 127.8, 127.6, 127.4 (d, 3JC–F = 3.0 Hz), 126.3, 121.6, 121.4 (d, J = 13.0 Hz), 21.6. 19F NMR (376 MHz, DMSO-d6): δ −117.96. HRMS (ESI) m/z: [M + H]+ calcd for C23H20FN2O4S+ [M + H]+, 437.0966; found, 437.0975.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-6-methylphenyl]-3H-quinazolin-4-one (3j)
The product is obtained as a white solid in 35% yield, 31 mg, mp 146–148 °C, Rf = 0.51 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.54 (s, 1H), 8.20 (d, J = 6.8 Hz, 1H), 7.88 (ddd, J = 7.6, 7.2, 1.6 Hz, 1H), 7.65–7.58 (m, 4H), 7.51–7.43 (m, 3H), 7.34 (d, J = 8.4 Hz, 2H), 6.77 (d, J = 19.6 Hz, 1H), 2.39 (s, 3H), 2.18 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 161.8, 153.2, 150.7 (d, 1JC–F = 253.0 Hz), 148.9, 146.4, 137.6, 135.0, 132.9, 132.8, 131.5, 130.7, 130.2, 128.0, 127.9, 127.5, 127.3, 126.4, 126.0 (d, 3JC–F = 5.0 Hz), 121.5 (d, 2JC–F = 17.0 Hz), 121.3, 21.7, 19.4. 19F NMR (376 MHz, DMSO-d6): δ −118.22. HRMS (ESI) m/z: [M + H]+ calcd for C24H20FN2O4S+ [M + H]+, 451.1122; found, 451.1225.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-6-methyloxylphenyl]-3H-quinazolin-4-one (3k)
The product is obtained as a white solid in 87% yield, 81 mg, mp 178–180 °C, Rf = 0.50 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.46 (s, 1H), 8.20 (d, J = 7.6 Hz, 1H), 7.86 (t, J = 7.6 Hz, 1H), 7.66–7.51 (m, 5H), 7.34 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.4 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H), 6.86 (d, J = 20.0 Hz, 1H), 3.78 (s, 3H), 2.38 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 161.8, 158.0, 151.4, 150.3 (d, 1JC–F = 254.0 Hz), 149.1, 146.5, 134.9, 131.8, 131.5, 130.7, 128.6 (d, 2JC–F = 22.0 Hz), 128.0, 127.8, 127.4, 126.3, 122.4, 121.7, 121.6 (d, 2JC–F = 13.0 Hz), 120.2 (d, 3JC–F = 5.0 Hz), 114.3, 56.6, 21.6. 19F NMR (376 MHz, DMSO-d6): δ −118.87. HRMS (ESI) m/z: [M + H]+ calcd for C24H20FN2O5S+ [M + H]+, 467.1072; found, 467.1077.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-6-ethyloxylphenyl]-3H-quinazolin-4-one (3l)
The product is obtained as a white solid in 86% yield, 83 mg, mp 151–153 °C, Rf = 0.48 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.45 (s, 1H), 8.21 (d, J = 7.6 Hz, 1H), 7.85 (t, J = 7.6 Hz, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.62–7.49 (m, 3H), 7.35 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 1H), 7.19 (d, J = 7.6 Hz, 1H), 6.88 (d, J = 20.0 Hz, 1H), 4.07 (q, J = 7.0 Hz, 2H), 2.38 (s, 3H), 1.16 (t, J = 7.0 Hz, 3H). 13C NMR (101 MHz, DMSO-d6): δ 161.8, 157.4, 151.5, 150.4 (d, 1JC–F = 253.0 Hz), 149.2, 146.4, 134.8, 131.8, 131.5, 130.7, 128.6 (d, 2JC–F = 22.0 Hz), 128.1, 127.8, 127.3, 126.3, 122.7, 121.7, 121.5 (d, 2JC–F = 13.0 Hz), 120.2 (d, 3JC–F = 5.0 Hz), 115.4, 64.9, 21.6, 14.8. 19F NMR (376 MHz, DMSO-d6): δ −118.71. HRMS (ESI) m/z: [M + H]+ calcd for C25H22FN2O5S+ [M + H]+, 481.1228; found, 481.1230.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-5-methylphenyl]-3H-quinazolin-4-one (3m)
The product is obtained as a white solid in 30% yield, 27 mg, mp 168–170 °C, Rf = 0.53 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.53 (s, 1H), 8.18 (dd, J = 8.0, 1.2 Hz, 1H), 7.85 (ddd, J = 8.4, 6.8, 1.6 Hz, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.57 (ddd, J = 8.0, 6.8, 1.2 Hz, 1H), 7.53–7.48 (m, 3H), 7.34 (s, 1H), 7.39 (d, J = 8.4 Hz, 1H), 6.83 (d, J = 20.0 Hz, 1H), 2.40 (s, 6H). 13C NMR (101 MHz, DMSO-d6): δ 162.0, 153.7, 151.0 (d, 1JC–F = 253.0 Hz), 148.9, 146.4, 140.9, 1350.0, 133.2, 131.7, 131.2, 131.1, 130.7, 129.1 (d, 3J = 3.0 Hz), 128.2, 127.8, 127.3, 126.3, 124.7 (d, 2JC–F = 22.0 Hz), 121.5, 120.9 (d, 2JC–F = 13.0 Hz), 21.7, 21.2. 19F NMR (376 MHz, DMSO-d6): δ −117.45. HRMS (ESI) m/z: [M + H]+ calcd for C24H20FN2O4S+ [M + H]+, 451.1122; found, 451.1120.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-5-chlorophenyl]-3H-quinazolin-4-one (3o)
The product is obtained as a pale yellow solid in 65% yield, 61 mg, mp 187–189 °C, Rf = 0.55 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.63 (s, 1H), 8.19 (d, J = 8.0 Hz, 1H), 7.85 (t, J = 7.6 Hz, 1H), 7.81 (d, J = 7.6 Hz, 1H), 7.74 (d, J = 8.0 Hz, 2H), 7.71–7.63 (m, 2H), 7.58 (t, J = 7.6 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.40 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 19.6 Hz, 1H), 2.40 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 161.9, 152.3, 149.9 (d, 1JC–F = 253.0 Hz), 148.7, 146.5, 135.4, 135.0, 134.8, 131.6, 130.9 (d, 3JC–F = 5.0 Hz), 130.8, 130.6 (d, 2JC–F = 13.0 Hz), 128.2, 128.1 (d, 3JC–F = 6.0 Hz), 127.9, 127.6, 126.5, 126.3, 121.9 (d, 2JC–F = 12.0 Hz), 121.7, 21.7. 19F NMR (376 MHz, DMSO-d6): δ −118.90. HRMS (ESI) m/z: [M + H]+ calcd for C23H17ClFN2O4S+ [M + H]+, 471.0576; found, 471.0573.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-5-fluorophenyl]-3H-quinazolin-4-one (3p)
The product is obtained as a pale yellow solid in 65% yield, 59 mg, mp 191–192 °C, Rf = 0.54 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.65 (s, 1H), 8.20 (dd, J = 8.0, 1.2 Hz, 1H), 7.86 (ddd, J = 8.4, 6.8, 1.2 Hz, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.72–7.57 (m, 3H), 7.53–7.47 (m, 2H), 7.41 (d, J = 8.0 Hz, 2H), 6.94 (d, J = 19.6 Hz, 1H), 2.41 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 162.9 (d, 1JC–F = 248.0 Hz), 161.9, 152.3, 150.1 (d, 1JC–F = 254.0 Hz), 148.7, 146.5, 135.6 (d, 3JC–F = 8.0 Hz), 135.0, 132.0 (dd, 33J = 8.0, 4.0 Hz), 131.6, 130.8, 128.2, 127.8, 127.6, 126.3, 124.2 (dd, 24JC–F = 23.0, 3.0 Hz), 121.6, 121.4 (d, 2JC–F = 13.0 Hz), 118.0 (d, 2JC–F = 18.0 Hz), 117.8 (d, 2JC–F = 16.0 Hz), 21.7. 19F NMR (376 MHz, DMSO-d6): δ −109.37, −117.14. HRMS (ESI) m/z: [M + H]+ calcd for C23H17F2N2O4S+ [M + H]+, 455.0872; found, 455.0879.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-phenyl]-6-methyloxyl-3H-quinazolin-4-one (3q)
The product is obtained as a white solid, 82 mg, 88% yield, mp 209–210 °C, Rf = 0.40 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.54 (s, 1H), 7.75 (d, J = 8.0 Hz, 2H), 7.68–7.55 (m, 5H), 7.50–7.36 (m, 4H), 6.88 (d, J = 19.6 Hz, 1H), 3.91 (s, 3H), 2.39 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 161.8, 158.5, 151.2, 152.0 (d, 1JC–F = 254.0 Hz), 146.4, 143.4, 133.4, 131.6, 130.8, 130.7, 130.6 (d, 3JC–F = 5.0 Hz), 129.5, 129.2 (d, 3JC–F = 5.0 Hz), 128.2, 127.5 (d, 2JC–F = 22.0 Hz), 124.3, 122.4, 121.3 (d, 2JC–F = 12.0 Hz), 106.4, 56.2, 21.6. 19F NMR (376 MHz, DMSO-d6): δ −117.94. HRMS (ESI) m/z: [M + H]+ calcd for C24H20FN2O5S+ [M + H]+, 467.1072; found, 467.1077.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-4-methylphenyl]-6-methyloxyl-3H-quinazolin-4-one (3r)
The product is obtained as a white solid, 1 mg, 86% yield, mp 205–207 °C, Rf = 0.41 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.49 (s, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.58–7.51 (m, 2H), 7.46–7.37 (m, 6H), 6.87 (d, J = 19.6 Hz, 1H), 3.91 (s, 3H), 2.39 (s, 6H). 13C NMR (101 MHz, DMSO-d6): δ 161.9, 158.4, 151.3, 151.1 (d, 1JC–F = 254.0 Hz), 146.4, 143.4, 140.6, 131.7, 131.3, 130.8, 130.7, 130.5, 129.6 (d, 3JC–F = 4.0 Hz), 129.5, 128.2, 127.4 (d, 2JC–F = 22.0 Hz), 124.3, 122.3, 121.2 (d, 2JC–F = 13.0 Hz), 106.4, 56.2, 21.6, 21.1. 19F NMR (376 MHz, DMSO-d6): δ −117.76. HRMS (ESI) m/z: [M + H]+ calcd for C25H22FN2O5S+ [M + H]+, 481.1228; found, 481.1232.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-4-methyloxylphenyl]-6-methyloxyl-3H-quinazolin-4-one (3s)
The product is obtained as a white solid, 85 mg, 86% yield, mp 201–202 °C, Rf = 0.42 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.44 (s, 1H), 7.75 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 8.8 Hz, 1H), 7.55 (s, 1H), 7.46–7.36 (m, 4H), 7.15 (dd, J = 8.8, 2.4 Hz, 1H), 7.08 (d, J = 2.4 Hz, 1H), 6.92 (d, J = 19.6 Hz, 1H), 3.90 (s, 3H), 3.86 (s, 3H), 2.39 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 162.0, 160.6, 158.3, 151.1, 150.9 (d, 1JC–F = 253.0 Hz), 146.5, 143.5, 132.2, 131.6, 130.8, 129.4, 129.1 (d, 2JC–F = 22.0 Hz), 128.2, 125.7, 124.3, 122.2, 121.5 (d, 2JC–F = 12.0 Hz), 116.1, 114.7 (d, 3JC–F = 5.0 Hz), 106.3, 56.2, 56.1, 21.6. 19F NMR (376 MHz, DMSO-d6): δ −117.63. HRMS (ESI) m/z: [M + H]+ calcd for C25H22FN2O6S+ [M + H]+, 497.1177; found, 497.1180.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-phenyl]-6-chloro-3H-quinazolin-4-one (3t)
The product is obtained as a white solid, 82 mg, 87% yield, mp 219–220 °C, Rf = 0.42 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.80 (s, 1H), 8.11 (d, J = 2.4 Hz, 1H), 7.86 (dd, J = 8.8, 2.4 Hz, 1H), 7.76 (d, J = 8.0 Hz, 2H), 7.71–7.60 (m, 4H), 7.54 (d, J = 8.8 Hz, 1H), 7.41 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 19.6 Hz, 1H), 2.40 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 161.1, 154.2, 150.8 (d, 1JC–F = 254.0 Hz), 147.6, 146.5, 135.1, 133.0, 131.7, 131.6, 130.9, 130.8, 130.7, 130.6, 130.0, 129.2 (d, 3JC–F = 4.0 Hz), 128.2, 127.5 (d, 2JC–F = 22.0 Hz), 125.3, 122.8, 121.4 (d, 2JC–F = 13.0 Hz), 21.6. 19F NMR (376 MHz, DMSO-d6): δ −117.92. HRMS (ESI) m/z: [M + H]+ calcd for C23H17ClFN2O4S+ [M + H]+, 471.0576; found, 471.0583.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-4-methylphenyl]-6-chloro-3H-quinazolin-4-one (3u)
The product is obtained as a white solid, 83 mg, 86% yield, mp 200–201 °C, Rf = 0.39 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.73 (s, 1H), 8.09 (d, J = 2.4 Hz, 1H), 7.85 (dd, J = 8.8, 2.4 Hz, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.4 Hz, 1H), 7.51 (d, J = 8.4 Hz, 1H), 7.44–7.40 (m, 4H), 6.85 (d, J = 19.6 Hz, 1H), 2.40 (s, 6H). 13C NMR (101 MHz, DMSO-d6): δ 161.2, 154.1, 151 (d, 1JC–F = 253.0 Hz), 147.6, 146.5, 141.0, 135.1, 131.6, 131.6, 131.4, 130.8, 130.5, 130.2, 130.0, 129.6, 128.2, 127.4 (d, 2JC–F = 21.0 Hz), 125.3, 122.6, 121.2 (d, 2JC–F = 12.0 Hz), 21.6, 21.1. 19F NMR (376 MHz, DMSO-d6): δ −117.71. HRMS (ESI) m/z: [M + H]+ calcd for C24H19ClFN2O4S+ [M + H]+, 485.0733; found, 485.0743.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-4-methyloxylphenyl]-6-chloro-3H-quinazolin-4-one (3v)
The product is obtained as a white solid, 83 mg, 83% yield, mp 181–183 °C, Rf = 0.40 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.70 (s, 1H), 8.08 (d, J = 2.0 Hz, 1H), 7.83 (dd, J = 8.4, 2.4 Hz, 1H), 7.79 (d, J = 8.0 Hz, 2H), 7.62 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 8.8 Hz, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.17 (dd, J = 8.4, 2.0 Hz, 1H), 7.12 (s, 1H), 6.98 (d, J = 19.6 Hz, 1H), 3.87 (s, 3H), 2.41 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 161.3, 160.9, 153.9, 150.7 (d, 1JC–F = 253.0 Hz), 147.5, 146.5, 135.0, 132.3, 131.6, 131.5, 130.7, 129.8, 129.2 (d, 2JC–F = 22.0 Hz), 128.2, 125.3, 125.2, 122.5, 121.5 (d, 2JC–F = 12.0 Hz), 116.1, 114.8 (d, 3JC–F = 4.0 Hz), 56.2, 21.6. 19F NMR (376 MHz, DMSO-d6): δ −117.45. HRMS (ESI) m/z: [M + H]+ calcd for C24H19ClFN2O5S+ [M + H]+, 501.0682; found, 501.0672.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-phenyl]-6-bromo-3H-quinazolin-4-one (3w)
82 mg, 80% yield, white solid, mp 217–219 °C, Rf = 0.39 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.80 (s, 1H), 8.26 (d, J = 2.4 Hz, 1H), 8.00 (dd, J = 8.8, 2.4 Hz, 1H), 7.76 (d, J = 8.0 Hz, 2H), 7.70–7.60 (m, 4H), 7.47 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 19.6 Hz, 1H), 2.41 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 160.9, 154.2, 150.8 (d, 1JC–F = 254.0 Hz), 147.9, 146.5, 137.8, 133.0, 131.6, 130.9, 130.8, 130.7, 130.5, 130.2, 129.2 (d, 3J = 4.0 Hz), 128.4, 128.2, 127.5 (d, 2JC–F = 22.0 Hz), 123.1, 121.4 (d, 2JC–F = 12.0 Hz), 119.8, 21.7. 19F NMR (376 MHz, DMSO-d6): δ −117.91. HRMS (ESI) m/z: [M + H]+ calcd for C23H17BrFN2O4S+ [M + H]+, 515.0071; found, 515.0076.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-4-methylphenyl]-6-bromo-3H-quinazolin-4-one (3x)
The product is obtained as a white solid, 85 mg, 80% yield, mp 195–197 °C, Rf = 0.40 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.74 (s, 1H), 8.23 (s, 1H), 7.97 (dd, J = 8.4, 2.4 Hz, 1H), 7.80–7.66 (m, 2H), 7.56 (d, J = 7.6 Hz, 1H), 7.43 (dd, J = 10.0, 3.7 Hz, 5H), 6.88 (d, J = 19.6 Hz, 1H), 2.40 (s, 6H). 13C NMR (101 MHz, DMSO-d6): δ 161.0, 154.2, 151.0 (d, 1JC–F = 254.0 Hz), 147.9, 146.4, 141.0, 137.8, 131.7, 131.3, 130.7, 130.5, 130.3, 130.1, 129.6 (d, 3J = 4.0 Hz), 128.4, 128.2, 127.4 (d, 2JC–F = 22.0 Hz), 123.0, 121.2 (d, 2JC–F = 13.0 Hz), 119.7, 21.6, 21.1. 19F NMR (376 MHz, DMSO-d6): δ −117.69. HRMS (ESI) m/z: [M + H]+ calcd for C24H19BrFN2O4S+ [M + H]+, 529.0228; found, 529.0233.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-phenyl]-7-methyl-3H-quinazolin-4-one (3y)
The product is obtained as a white solid, 77 mg, 85% yield, mp 212–213 °C, Rf = 0.41 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.51 (s, 1H), 8.08 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 8.0 Hz, 2H), 7.70–7.56 (m, 4H), 7.39–7.37 (m, 4H), 6.91 (d, J = 19.6 Hz, 1H), 2.47 (s, 3H), 2.37 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 161.9, 153.7, 150.9 (d, 1JC–F = 254.0 Hz), 149.1, 146.4, 145.5, 133.4, 131.6, 130.9, 130.7, 130.5, 129.1 (d, 3JC–F = 5.0 Hz), 128.8, 128.2, 127.5 (d, 2JC–F = 21.0 Hz), 127.4, 126.2, 121.4 (d, 2JC–F = 13.0 Hz), 119.2, 21.8, 21.6. 19F NMR (376 MHz, DMSO-d6): δ −117.98. HRMS (ESI) m/z: [M + H]+ calcd for C24H20FN2O4S+ [M + H]+, 451.1122; found, 451.1119.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-4-methylphenyl]-7-methyl-3H-quinazolin-4-one (3z)
The product is obtained as a white solid, 79 mg, 85% yield, mp 204–206 °C, Rf = 0.39 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.46 (s, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.76 (d, J = 8.0 Hz, 2H), 7.53 (d, J = 7.6 Hz, 1H), 7.45–7.33 (m, 6H), 6.89 (d, J = 19.6 Hz, 1H), 2.46 (s, 3H), 2.39 (d, J = 6.8 Hz, 6H). 13C NMR (101 MHz, DMSO-d6): δ 162.0, 153.7, 151.1 (d, 1JC–F = 254.0 Hz), 149.0, 146.4, 145.5, 140.7, 131.7, 131.3, 130.7, 130.6, 130.5, 129.5 (d, 3JC–F = 5.0 Hz), 128.7, 128.2, 127.4 (d, 2J = 21.0 Hz), 127.3, 126.2, 121.2 (d, 2JC–F = 13.0 Hz), 119.1, 21.8, 21.6, 21.1. 19F NMR (376 MHz, DMSO-d6): δ −117.83. HRMS (ESI) m/z: [M + H]+ calcd for C25H22FN2O4S+ [M + H]+, 465.1279; found, 465.1286.
2-[2-(1-Fluoro-2-p-methylbenzenesulfonyloxyl-vinyl)-4-methyloxylphenyl]-7-methyl-3H-quinazolin-4-one (3za)
The product is obtained as a white solid, 80 mg, 83% yield, mp 196–198 °C, Rf = 0.39 (petroleum ether/ethyl acetate = 2/1). 1H NMR (400 MHz, DMSO-d6): δ 12.40 (s, 1H), 8.05 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.60 (d, J = 8.4 Hz, 1H), 7.44–7.29 (m, 4H), 7.16 (dd, J = 8.4, 2.0 Hz, 1H), 7.10 (s, 1H), 6.98 (d, J = 19.6 Hz, 1H), 3.87 (s, 3H), 2.46 (s, 3H), 2.38 (s, 3H). 13C NMR (101 MHz, DMSO-d6): δ 162.1, 160.7, 153.5, 150.8 (d, 1JC–F = 254.0 Hz), 149.2, 146.4, 145.4, 132.2, 131.7, 130.7, 129.1 (d, 2JC–F = 22.0 Hz), 128.6, 128.2, 127.3, 126.1, 125.8, 121.5 (d, 2JC–F = 12.0 Hz), 119.0, 116.1, 114.7 (d, 3JC–F = 5.0 Hz), 56.2, 21.8, 21.6. 19F NMR (376 MHz, DMSO-d6): δ −117.64. HRMS (ESI) m/z: [M + H]+ calcd for C25H22FN2O5S+ [M + H]+, 481.1228; found, 481.1232.
Acknowledgments
Financial support from the National Natural Science Foundation of China (nos. 21762020 and 21362014), the Jiangxi Provincial Department of Science and Technology (no. 20171BAB203006), and the Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Jiangxi Normal University (no. KLFS-KF-201623) is gratefully acknowledged.
Supporting Information Available
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.0c01344.
The authors declare no competing financial interest.
Supplementary Material
References
- Review see:; a Zhou Y.; Wang J.; Gu Z.; Wang S.; Zhu W.; Aceña J. L.; Soloshonok V. A.; Izawa K.; Liu H. Next generation of fluorine-containing pharmaceuticals, compounds currently in phase II-III clinical trials of major pharmaceutical companies: New structural trends and therapeutic areas. Chem. Rev. 2016, 116, 422–518. 10.1021/acs.chemrev.5b00392. [DOI] [PubMed] [Google Scholar]; b Gillis E. P.; Eastman K. J.; Hill M. D.; Donnelly D. J.; Meanwell N. A. Applications of fluorine in medicinal chemistry. J. Med. Chem. 2015, 58, 8315–8359. 10.1021/acs.jmedchem.5b00258. [DOI] [PubMed] [Google Scholar]; c Fujiwara T.; O’Hagan D. Successful fluorine-containing herbicide agrochemicals. J. Fluorine Chem. 2014, 167, 16–29. 10.1016/j.jfluchem.2014.06.014. [DOI] [Google Scholar]; d Wang J.; Sánchez-Roselló M.; Aceña J. L.; del Pozo C.; Sorochinsky A. E.; Fustero S.; Soloshonok V. A.; Liu H. Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001-2011). Chem. Rev. 2014, 114, 2432–2506. 10.1021/cr4002879. [DOI] [PubMed] [Google Scholar]; e Berger R.; Resnati G.; Metrangolo P.; Weber E.; Hulliger J. Organic fluorine compounds: a great opportunity for enhanced materials properties. Chem. Soc. Rev. 2011, 40, 3496–3508. 10.1039/c0cs00221f. [DOI] [PubMed] [Google Scholar]; f Jeschke P. The unique role of halogen substituents in the design of modern agrochemicals. Pest Manage. Sci. 2010, 66, 10–27. 10.1002/ps.1829. [DOI] [PubMed] [Google Scholar]; g Purser S.; Moore P. R.; Swallow S.; Gouverneur V. Fluorine in medicinal chemistry. Chem. Soc. Rev. 2008, 37, 320–330. 10.1039/b610213c. [DOI] [PubMed] [Google Scholar]; h Hagmann W. K. The many roles for fluorine in medicinal chemistry. J. Med. Chem. 2008, 51, 4359–4369. 10.1021/jm800219f. [DOI] [PubMed] [Google Scholar]; i Babudri F.; Farinola G. M.; Naso F.; Ragni R. Fluorinated organic materials for electronic and optoelectronic applications: the role of the fluorine atom. Chem. Commun. 2007, 1003–1022. 10.1039/b611336b. [DOI] [PubMed] [Google Scholar]; j Jeschke P. The unique role of fluorine in the design of active ingredients for modern crop protection. ChemBioChem 2004, 5, 570–589. 10.1002/cbic.200300833. [DOI] [PubMed] [Google Scholar]; k Müller K.; Faeh C.; Diederich F. Fluorine in pharmaceuticals: Looking beyond intuition. Science 2007, 317, 1881–1886. 10.1126/science.1131943. [DOI] [PubMed] [Google Scholar]; l Pagliaro M.; Ciriminna R. New fluorinated functional materials. J. Mater. Chem. 2005, 15, 4981–4991. 10.1039/b507583c. [DOI] [Google Scholar]; m Rosen T. C.; Yoshida S.; Kirk K. L.; Haufe G. Fluorinated phenylcyclopropylamines as inhibitors of monoamine oxidases. ChemBioChem 2004, 5, 1033–1043. 10.1002/cbic.200400053. [DOI] [PubMed] [Google Scholar]
- For reviews:; a Berger R.; Resnati G.; Metrangolo P.; Weber E.; Hulliger J. Organic fluorine compounds: a great opportunity for enhanced materials properties. Chem. Soc. Rev. 2011, 40, 3496–3508. 10.1039/c0cs00221f. [DOI] [PubMed] [Google Scholar]; b Champagne P. A.; Desroches J.; Hamel J.-D.; Vandamme M.; Paquin J.-F. Monofluorination of organic compounds: 10 Years of innovation. Chem. Rev. 2015, 115, 9073–9174. 10.1021/cr500706a. [DOI] [PubMed] [Google Scholar]; c Taguchi T.; Yanai H. in Fluorine in Medicinal Chemistry and Chemical Biology; Ojima I., Ed.; Wiley-Blackwell: Chichester, 2009; pp 257–290. [Google Scholar]
- a Aldoshin A. S.; Tabolin A. A.; Ioffe S. L.; Nenajdenko V. G. Green, catalyst-free reaction of indoles with β-fluoro-β-nitrostyrenes in water. Eur. J. Org. Chem. 2018, 3816–3825. 10.1002/ejoc.201800385. [DOI] [Google Scholar]; b Zhang H.; Zhou C.-B.; Chen Q.-Y.; Xiao J.-C.; Hong R. Monofluorovinyl tosylate: a useful building block for the synthesis of terminal vinyl monofluorides via Suzuki-Miyaura coupling. Org. Lett. 2010, 13, 560–563. 10.1021/ol102645g. [DOI] [PubMed] [Google Scholar]; c Drouin M.; Paquin J.-F. Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres. Beilstein J. Org. Chem. 2017, 13, 2637–2658. 10.3762/bjoc.13.262. [DOI] [PMC free article] [PubMed] [Google Scholar]; d Der Veken P. V.; Senten K.; Kertèsz I.; De Meester I.; Lambeir A.-M.; Maes M.-B.; Scharpé S.; Haemers A.; Augustyns K. Fluoro-Olefins as peptidomimetic inhibitors of dipeptidyl peptidases. J. Med. Chem. 2005, 48, 1768–1780. 10.1021/jm0495982. [DOI] [PubMed] [Google Scholar]; e Osada S.; Sano S.; Ueyama M.; Chuman Y.; Kodama H.; Sakaguchi K. Fluoroalkene modification of mercaptoacetamide-based histone deacetylase inhibitors. Bioorg. Med. Chem. 2010, 18, 605–611. 10.1016/j.bmc.2009.12.005. [DOI] [PubMed] [Google Scholar]; f Couve-Bonnaire S.; Cahard D.; Pannecoucke X. Chiral dipeptide mimics possessing a fluoroolefin moiety: a relevant tool for conformational and medicinal studies. Org. Biomol. Chem. 2007, 5, 1151–1157. 10.1039/b701559c. [DOI] [PubMed] [Google Scholar]; g Oishi S.; Kamitani H.; Kodera Y.; Watanabe K.; Kobayashi K.; Narumi T.; Tomita K.; Ohno H.; Naito T.; Kodama E.; Matsuoka M.; Fujii N. Peptide bond mimicry by (E)-alkene and (Z)-fluoroalkene peptide isosteres: synthesis and bioevaluation of a-helical anti-HIV peptide analogues. Org. Biomol. Chem. 2009, 7, 2872–2877. 10.1039/b907983a. [DOI] [PubMed] [Google Scholar]; h Edmondson S. D.; Wei L.; Xu J.; Shang J.; Xu S.; Pang J.; Chaudhary A.; Dean D. C.; He H.; Leiting B.; Lyons K. A.; Patel R. A.; Patel S. B.; Scapin G.; Wu J. K.; Beconi M. G.; Thornberry N. A.; Weber A. E. Fluoroolefins as amide bond mimics in dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett. 2008, 18, 2409–2413. 10.1016/j.bmcl.2008.02.050. [DOI] [PubMed] [Google Scholar]
- For reviews:; a Zhang X.; Cao S. Recent advances in the synthesis and C-F functionalization of gem-difluoroalkenes. Tetrahedron Lett. 2017, 58, 375–392. 10.1016/j.tetlet.2016.12.054. [DOI] [Google Scholar]; b Drouin M.; Hamel J.-D.; Paquin J.-F. Exploiting 3,3-difluoropropenes for the synthesis of monofluoroalkenes. Synlett 2017, 27, 821–830. [Google Scholar]; c Van Steenis J. H.; der Gen A. v. Synthesis of terminal monofluoro olefins. J. Chem. Soc., Perkin Trans. 1 2002, 2117–2133. 10.1039/b106187a. [DOI] [Google Scholar]; d Yanai H.; Taguchi T. Synthetic methods for fluorinated olefins. Eur. J. Org. Chem. 2011, 5939–5954. 10.1002/ejoc.201100495. [DOI] [Google Scholar]; e Landelle G.; Bergeron M.; Turcotte-Savard M.-O.; Paquin J.-F. Synthetic approaches to monofluoroalkenes. Chem. Soc. Rev. 2011, 40, 2867–2908. 10.1039/c0cs00201a. [DOI] [PubMed] [Google Scholar]; . For recent examples:; f Tan D.-H.; Lin E.; Ji W.-W.; Zeng Y.-F.; Fan W.-X.; Li Q.; Gao H.; Wang H. Copper-catalyzed stereoselective defluorinative borylation and silylation of gem-difluoroalkenes. Adv. Synth. Catal. 2018, 360, 1032–1037. 10.1002/adsc.201701497. [DOI] [Google Scholar]; g Yang H.; Tian C.; Qiu D.; Tian H.; An G.; Li G. Organic photoredox catalytic decarboxylative cross-coupling of gem-difluoroalkenes with unactivated carboxylic acids. Org. Chem. Front. 2019, 6, 2365–2370. 10.1039/c9qo00495e. [DOI] [Google Scholar]; h Jiang L.-F.; Ren B.-T.; Li B.; Zhang G.-Y.; Peng Y.; Guan Z.-Y.; Deng Q.-H. Nucleophilic substitution of gem-difluoroalkenes with TMSNu promoted by catalytic amounts of Cs2CO3. J. Org. Chem. 2019, 84, 6557–6564. 10.1021/acs.joc.9b00999. [DOI] [PubMed] [Google Scholar]; i Jayaraman A.; Lee S. Silver-Mediated decarboxylative fluorodiiodination of alkynoic acids: synthesis of regio- and stereoselective fluoroalkenes. Org. Lett. 2019, 21, 3485–3489. 10.1021/acs.orglett.9b00597. [DOI] [PubMed] [Google Scholar]; j He Y.; Anand D.; Sun Z.; Zhou L. Visible-light-promoted redox neutral γ,γ-difluoroallylation of cycloketone oxime ethers with trifluoromethyl alkenes via C-C and C-F bond cleavage. Org. Lett. 2019, 21, 3769–3773. 10.1021/acs.orglett.9b01210. [DOI] [PubMed] [Google Scholar]; k Tian H.; Xia Q.; Wang Q.; Dong J.; Liu Y.; Wang Q. Direct α-monofluoroalkenylation of heteroatomic alkanes via a combination of photoredox catalysis and hydrogen-atom-transfer catalysis. Org. Lett. 2019, 21, 4585–4589. 10.1021/acs.orglett.9b01491. [DOI] [PubMed] [Google Scholar]; l Yang L.; Ji W.-W.; Lin E.; Li J.-L.; Fan W.-X.; Li Q.; Wang H. Synthesis of alkylated monofluoroalkenes via Fe-catalyzed defluorinative cross-coupling of donor alkenes with gem-difluoroalkenes. Org. Lett. 2018, 20, 1924–1927. 10.1021/acs.orglett.8b00471. [DOI] [PubMed] [Google Scholar]; m Thornbury R. T.; Toste F. D. Palladium-catalyzed defluorinative coupling of 1-aryl-2,2-difluoroalkenes and boronic acids: stereoselective synthesis of monofluorostilbenes. Angew. Chem., Int. Ed. 2016, 55, 11629–11632. 10.1002/anie.201605651. [DOI] [PMC free article] [PubMed] [Google Scholar]; n Zhang X.; Lin Y.; Zhang J.; Cao S. Base-mediated direct fluoroalkenylation of 2-phenyl-1,3,4-oxadiazole, benzothiazole and benzoxazole with gem-difluoroalkenes. RSC Adv. 2015, 5, 7905–7908. 10.1039/c4ra13761b. [DOI] [Google Scholar]; o Xiong Y.; Huang T.; Ji X.; Wu J.; Cao S. Nickel-catalyzed Suzuki-Miyaura type crosscoupling reactions of (2,2-difluorovinyl)benzene derivatives with arylboronic acids. Org. Biomol. Chem. 2015, 13, 7389–7392. 10.1039/c5ob01016k. [DOI] [PubMed] [Google Scholar]
- a Li N.; Chang J.; Kong L.; Li X. Ruthenium(II)-catalyzed α-fluoroalkenylation of arenes via C-H bond activation and C-F bond cleavage. Org. Chem. Front. 2018, 5, 1978–1982. 10.1039/c8qo00297e. [DOI] [Google Scholar]; b Zell D.; Dhawa U.; Müller V.; Bursch M.; Grimme S.; Ackermann L. C-F/C-H functionalization by manganese (I) catalysis: expedient (per)fluoro-allylations and alkenylations. ACS Catal. 2017, 7, 4209–4213. 10.1021/acscatal.7b01208. [DOI] [Google Scholar]; c Kong L.; Liu B.; Zhou X.; Wang F.; Li X. Rhodium(III)-catalyzed regio- and stereoselective benzylic α-fluoroalkenylation with gem-difluorostyrenes. Chem. Commun. 2017, 53, 10326–10329. 10.1039/c7cc06048c. [DOI] [PubMed] [Google Scholar]; d Cai S.-H.; Ye L.; Wang D.-X.; Wang Y.-Q.; Lai L.-J.; Zhu C.; Feng C.; Loh T.-P. Manganese-catalyzed synthesis of monofluoroalkenes via C-H activation and C-F cleavage. Chem. Commun. 2017, 53, 8731–8734. 10.1039/c7cc04131d. [DOI] [PubMed] [Google Scholar]; e Zell D.; Müller V.; Dhawa U.; Bursch M.; Presa R. R.; Grimme S.; Ackermann L. Mild Cobalt(III)-catalyzed allylative C-F/C-H functionalizations at room temperature. Chem.—Eur. J. 2017, 23, 12145–12148. 10.1002/chem.201702528. [DOI] [PubMed] [Google Scholar]; f Kong L.; Zhou X.; Li X. Cobalt(III)-catalyzed regio- and stereoselective α-fluoroalkenylation of arenes with gem-difluorostyrenes. Org. Lett. 2016, 18, 6320–6323. 10.1021/acs.orglett.6b03203. [DOI] [PubMed] [Google Scholar]; g Liu H.; Song S.; Wang C.-Q.; Feng C.; Loh T.-P. Redox-neutral rhodium-catalyzed [4+1] annulation through formal dehydrogenative vinylidene insertion. ChemSusChem 2017, 10, 58–61. 10.1002/cssc.201601341. [DOI] [PubMed] [Google Scholar]; h Tian P.; Wang C.-Q.; Cai S.-H.; Song S.; Ye L.; Feng C.; Loh T.-P. F- nucleophilic-addition-induced allylic alkylation. J. Am. Chem. Soc. 2016, 138, 15869–15872. 10.1021/jacs.6b11205. [DOI] [PubMed] [Google Scholar]; i Tian P.; Feng C.; Loh T. P. Rhodium-catalysed C(sp2)-C(sp2) bond formation via C-H/C-F activation. Nat. Commun. 2015, 6, 7472–7479. 10.1038/ncomms8472. [DOI] [PMC free article] [PubMed] [Google Scholar]; j Rousée K.; Schneider C.; Couve-Bonnaire S.; Pannecoucke X.; Levacher V.; Hoarau C. Pd- and Cu-catalyzed stereo- and regiocontrolled decarboxylative/C-H fluoroalkenylation of heteroarenes. Chem.—Eur. J. 2014, 20, 15000–15004. 10.1002/chem.201405119. [DOI] [PubMed] [Google Scholar]; k Schneider C.; Masi D.; Couve-Bonnaire S.; Pannecoucke X.; Hoarau C. Palladium- and copper-catalyzed stereocontrolled direct C-H fluoroalkenylation of heteroarenes using gem-bromofluoroalkenes. Angew. Chem., Int. Ed. 2013, 52, 3246–3249. 10.1002/anie.201209446. [DOI] [PubMed] [Google Scholar]
- a Wu J.-Q.; Zhang S.-S.; Gao H.; Qi Z.; Zhou C.-J.; Ji W.-W.; Liu Y.; Chen Y.; Li Q.; Li X.; Wang H. Experimental and theoretical studies on rhodium-catalyzed coupling of benzamides with 2,2-difluorovinyl tosylate: diverse synthesis of fluorinated heterocycles. J. Am. Chem. Soc. 2017, 139, 3537–3545. 10.1021/jacs.7b00118. [DOI] [PubMed] [Google Scholar]; b Ji W.-W.; Lin E.; Li Q.; Wang H. Heteroannulation enabled by a bimetallic Rh(III)/Ag(I) relay catalysis: application in the total synthesis of aristolactam BII. Chem. Commun. 2017, 53, 5665–5668. 10.1039/c7cc02105d. [DOI] [PubMed] [Google Scholar]; c Tian M.; Yang X.; Zhang B.; Liu B.; Li X. Rh(III)-Catalyzed α-fluoroalkenylation of N-nitrosoanilines with 2,2-difluorovinyl tosylates via C-H bond activation. Org. Chem. Front. 2018, 5, 3406–3409. 10.1039/c8qo00947c. [DOI] [Google Scholar]; d Zhu C.; Song S.; Zhou L.; Wang D.-X.; Feng C.; Loh T.-P. Nonconventional difluoroalkylation of C(sp2)-H bonds through hydroarylation. Chem. Commun. 2017, 53, 9482–9485. 10.1039/c7cc04842d. [DOI] [PubMed] [Google Scholar]; e Zhou L.; Zhu C.; Loh T.-P.; Feng C. Rh-Catalyzed C-H bond alkylation of indoles with a,a-difluorovinyl tosylate via indolyl group migration. Chem. Commun. 2018, 54, 5618–5621. 10.1039/c8cc02183j. [DOI] [PubMed] [Google Scholar]; f Yang L.; Li C.; Wang D.; Liu H. Cp*Rh(III)-Catalyzed C-H bond difluorovinylation of indoles with α,α-difluorovinyl tosylate. J. Org. Chem. 2019, 84, 7320–7330. 10.1021/acs.joc.9b00957. [DOI] [PubMed] [Google Scholar]
- For selected reviews, see:; a Li S.-G.; Wang K.-B.; Gong C.; Bao Y.; Qin N.-B.; Li D.-H.; Li Z.-L.; Bai J.; Hua H.-M. Cytotoxic quinazoline alkaloids from the seeds of Peganum harmala. Bioorg. Med. Chem. Lett. 2018, 28, 103–106. 10.1016/j.bmcl.2017.12.003. [DOI] [PubMed] [Google Scholar]; b Shang X.-F.; Morris-Natschke S. L.; Liu Y.-Q.; Guo X.; Xu X.-S.; Goto M.; Li J.-C.; Yang G.-Z.; Lee K.-H. Biologically active quinoline and quinazoline alkaloids part I. Med. Res. Rev. 2018, 38, 775–828. 10.1002/med.21466. [DOI] [PMC free article] [PubMed] [Google Scholar]; c Michael J. P. Quinoline, quinazoline and acridone alkaloids. Nat. Prod. Rep. 2007, 24, 223–246. 10.1039/b509528j. [DOI] [PubMed] [Google Scholar]; d Mhaske S. B.; Argade N. P. The chemistry of recently isolated naturally occurring quinazolinone alkaloids. Tetrahedron 2006, 62, 9787–9826. 10.1016/j.tet.2006.07.098. [DOI] [Google Scholar]
- For recent reviews see:; a Gatadi S.; Lakshmi T. V.; Nanduri S. 4(3H)-Quinazolinone derivatives: Promising antibacterial drug leads. Eur. J. Med. Chem. 2019, 170, 157–172. 10.1016/j.ejmech.2019.03.018. [DOI] [PubMed] [Google Scholar]; b Hameed A.; Al-Rashida M.; Uroos M.; Ali S. A.; Arshia; Ishtiaq M.; Khan K. M. Quinazoline and quinazolinone as important medicinal scaffolds: a comparative patent review (2011-2016). Expert Opin. Ther. Pat. 2018, 28, 281–297. 10.1080/13543776.2018.1432596. [DOI] [PubMed] [Google Scholar]
- For recent reviews see:; a Maiden T. M. M.; Harrity J. P. A. Recent developments in transition metal catalysis for quinazolinone synthesis. Org. Biomol. Chem. 2016, 14, 8014–8025. 10.1039/c6ob01402j. [DOI] [PubMed] [Google Scholar]; b Kshirsagar U. A. Recent developments in the chemistry of quinazolinone alkaloids. Org. Biomol. Chem. 2015, 13, 9336–9352. 10.1039/c5ob01379h. [DOI] [PubMed] [Google Scholar]; c Demeunynck M.; Baussanne I. Survey of recent literature related to the biologically active 4(3H)-quinazolinones containing fused heterocycles. Curr. Med. Chem. 2013, 20, 794–814. 10.2174/092986713805076711. [DOI] [PubMed] [Google Scholar]; d Sharma P. C.; Kaur G.; Pahwa R.; Sharma A.; Rajak H. Quinazolinone analogs as potential therapeutic agents. Curr. Med. Chem. 2011, 18, 4786–4812. 10.2174/092986711797535326. [DOI] [PubMed] [Google Scholar]; e Connolly D. J.; Cusack D.; O’Sullivan T. P.; Guiry P. J. Synthesis of quinazolinones and quinazolines. Tetrahedron 2005, 61, 10153–10202. 10.1016/j.tet.2005.07.010. [DOI] [Google Scholar]; f Witt A.; Bergman J. Recent developments in the field of quinazoline chemistry. Curr. Org. Chem. 2003, 7, 659–677. 10.2174/1385272033486738. [DOI] [Google Scholar]; g Nefzi A.; Ostresh J. M.; Houghten R. A. The Current Status of heterocyclic combinatorial libraries. Chem. Rev. 1997, 97, 449–472. 10.1021/cr960010b. [DOI] [PubMed] [Google Scholar]
- For selected recent examples, see:; a Buchstaller H.-P.; Anlauf U.; Dorsch D.; Kuhn D.; Lehmann M.; Leuthner B.; Musil D.; Radtki D.; Ritzert C.; Rohdich F.; Schneider R.; Esdar C. Discovery and optimization of 2-arylquinazolin-4-ones into a potent and selective tankyrase inhibitor modulating wnt pathway activity. J. Med. Chem. 2019, 62, 7897–7909. 10.1021/acs.jmedchem.9b00656. [DOI] [PubMed] [Google Scholar]; b Liang Y.; Tan Z.; Jiang H.; Zhu Z.; Zhang M. Copper-catalyzed oxidative multicomponent annulation reaction for direct synthesis of quinazolinones via an imine-protection strategy. Org. Lett. 2019, 21, 4725–4728. 10.1021/acs.orglett.9b01608. [DOI] [PubMed] [Google Scholar]; c Arachchige P. T. K.; Yi C. S. Synthesis of quinazoline and quinazolinone derivatives via ligand promoted ruthenium-catalyzed dehydrogenative and deaminative coupling reaction of 2-aminophenyl Ketones and 2-aminobenzamides with amines. Org. Lett. 2019, 21, 3337–3341. 10.1021/acs.jmedchem.9b00656. [DOI] [PubMed] [Google Scholar]; d Garia A.; Jain N. Transition-metal-free synthesis of fused quinazolinones by oxidative cyclization of N-pyridylindoles. J. Org. Chem. 2019, 84, 9661–9670. 10.1021/acs.joc.9b01170. [DOI] [PubMed] [Google Scholar]; e Maiti S.; Kim J.; Park J.-H.; Nam D.; Lee J. B.; Kim Y.-J.; Kee J.-M.; Seo J. K.; Myung K.; Rohde J.-U.; Choe W.; Kwon H.-H.; Hong S. Y. Chemoselective trifluoroethylation reactions of quinazolinones and identification of photostability. J. Org. Chem. 2019, 84, 6737–6751. 10.1021/acs.joc.9b00470. [DOI] [PubMed] [Google Scholar]; f Rohokale R. S.; Kalshetti R. G.; Ramana C. V. Iridium(III)-catalyzed alkynylation of 2 (hetero)arylquinazolin-4-one scaffolds via C-H bond activation. J. Org. Chem. 2019, 84, 2951–2961. 10.1021/acs.joc.8b02738. [DOI] [PubMed] [Google Scholar]; g Li J.; Wang Z.-B.; Xu Y.; Lu X.-C.; Zhu S.-R.; Liu L. Catalyst-free cyclization of anthranils and cyclic amines: one-step synthesis of rutaecarpine. Chem. Commun. 2019, 55, 12072–12075. 10.1039/c9cc06160f. [DOI] [PubMed] [Google Scholar]; h An J.; Wang Y.; Zhang Z.; Zhao Z.; Zhang J.; Wang F. The synthesis of quinazolinones from olefins, CO, and amines over a heterogeneous Ru-clusters/ceria catalyst. Angew. Chem., Int. Ed. 2018, 57, 12308–12312. 10.1002/anie.201806266. [DOI] [PubMed] [Google Scholar]; i Xie L.; Lu C.; Jing D.; Ou X.; Zheng K. Metal-free synthesis of polycyclic quinazolinones enabled by a (NH4)2S2O8-promoted intramolecular oxidative cyclization. Eur. J. Org. Chem. 2019, 3649–3653. 10.1002/ejoc.201900469. [DOI] [Google Scholar]; j Hudson L.; Mui J.; Vázquez S.; Carvalho D. M.; Williams E.; Jones C.; Bullock A. N.; Hoelder S. Novel quinazolinone inhibitors of ALK2 flip between alternate binding modes: structure activity relationship, structural characterization, kinase profiling, and cellular proof of concept. J. Med. Chem. 2018, 61, 7261–7272. 10.1021/acs.jmedchem.8b00782. [DOI] [PMC free article] [PubMed] [Google Scholar]; k Yu X.; Gao L.; Jia L.; Yamamoto Y.; Bao M. Synthesis of quinazolin-4(3H) ones via the reaction of 2-halobenzamides with nitriles. J. Org. Chem. 2018, 83, 10352–10358. 10.1021/acs.joc.8b01460. [DOI] [PubMed] [Google Scholar]; l ViveKi A. B.; Mhaske S. B. Ruthenium-catalyzed regioselective alkenylation/tandem hydroamidative cyclization of unmasked quinazolinones using terminal alkynes. J. Org. Chem. 2018, 83, 8906–8913. 10.1021/acs.joc.8b01143. [DOI] [PubMed] [Google Scholar]; m Ward A.; Dong L.; Harris J. M.; Khanna K. K.; Al-Ejeh F.; Fairlie D. P.; Wiegmans A. P.; Liu L. Quinazolinone derivatives as inhibitors of homologous recombinase RAD51. Bioorg. Med. Chem. Lett. 2017, 27, 3096–3100. 10.1016/j.bmcl.2017.05.039. [DOI] [PubMed] [Google Scholar]; n Smith G. F.; Altman M. D.; et al. Identification of quinazoline based inhibitors of IRAK4 for the treatment of inflammation. Bioorg. Med. Chem. Lett. 2017, 27, 2721–2726. 10.1016/j.bmcl.2017.04.050. [DOI] [PubMed] [Google Scholar]; o Hrast M.; Rožman K.; Jukič M.; Patin D.; Gobec S.; Sova M. Synthesis and structure activity relationship study of novel quinazolinone-based inhibitors of MurA. Bioorg. Med. Chem. Lett. 2017, 27, 3529–3533. 10.1016/j.bmcl.2017.05.064. [DOI] [PubMed] [Google Scholar]
- a Yan Z.; Ouyang B.; Mao X.; Gao W.; Deng Z.; Peng Y. One-pot regioselective C-H activation iodination cyanation of 2,4-diarylquinazolines using malononitrile as a cyano source. RSC Adv. 2019, 9, 18256–18264. 10.1039/c9ra02979f. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Lou M.; Deng Z.; Mao X.; Fu Y.; Yang Q.; Peng Y. Rhodium-catalyzed C–H bond activation alkylation and cyclization of 2-arylquinazolin-4-one. Org. Biomol. Chem. 2018, 16, 1851–1859. 10.1039/c8ob00147b. [DOI] [PubMed] [Google Scholar]; c Zhang Y.; Huang J.; Deng Z.; Mao X.; Peng Y. Rhodium(III)-catalyzed C–H amination of 2-arylquinazolin-4(3H)-one with N-alkyl-O-benzoyl-hydroxylamines. Tetrahedron 2018, 74, 2330–2337. 10.1016/j.tet.2018.03.051. [DOI] [Google Scholar]; d Zhou J.; Liu L.; Pan Y.; Zhu Q.; Lu Y.; Wei J.; Luo K.; Fu Y.; Zhong C.; Peng Y.; Song Z. Asymmetric difluoroboron quinazolinone-pyridine dyes with large stokes shift: high emission efficiencies both in solution and in the solid state. Chem.—Eur. J. 2018, 24, 17897–17901. 10.1002/chem.201803428. [DOI] [PubMed] [Google Scholar]; e Wei M.; Chai W.-M.; Wang R.; Yang Q.; Deng Z.; Peng Y. Quinazolinone derivatives: Synthesis and comparison of inhibitory mechanisms on α-glucosidase. Bioorg. Med. Chem. 2017, 25, 1303–1308. 10.1016/j.bmc.2016.09.042. [DOI] [PubMed] [Google Scholar]; f Jiang X.; Yang Q.; Yuan J.; Deng Z.; Mao X.; Peng Y.; Yu C. Rhodium-catalyzed tandem C-H activation and aza-Michael addition of 2-arylquinazolin-4-ones with acrylates for the synthesis of pyrrolo[2,1-b]quinazolin-9(1H)-one derivatives. Tetrahedron 2016, 72, 1238–1243. 10.1016/j.tet.2016.01.020. [DOI] [Google Scholar]; g Wang R.; Chai W.-M.; Yang Q.; Wei M.-K.; Peng Y. 2-(4-Fluorophenyl)-quinazolin-4(3H)-one as a novel tyrosinase inhibitor: synthesis, inhibitory activity, and mechanism. Bioorg. Med. Chem. 2016, 24, 4620–4625. 10.1016/j.bmc.2016.07.068. [DOI] [PubMed] [Google Scholar]; h Peng Y.; Chen X.; Yang Q.; Zhou Y.; Deng Z.; Mao X.; Peng Y. Synthesis of 4-(dimethylamino)quinazoline via direct amination of quinazolin-4(3H)-one using N,N-dimethylformamide as a nitrogen source at room temperature. Synthesis 2015, 47, 2055–2062. 10.1055/s-0034-1380550. [DOI] [Google Scholar]; i Zhao Y.; Liu W.; Li Q.; Yang Q.; Chai W.; Zeng M.; Li R.; Peng Y. Multiparameter-based bioassay of 2-(4-chlorophenyl)-4-(4-methoxyphenyl)quinazoline, a newly-synthesized quinazoline derivative, toward microcystis aeruginosa HAB5100 (cyanobacteria). Bull. Environ. Contam. Toxicol. 2015, 94, 376–381. 10.1007/s00128-015-1459-y. [DOI] [PubMed] [Google Scholar]; j Lu H.; Yang Q.; Zhou Y.; Guo Y.; Deng Z.; Ding Q.; Peng Y. Cross-coupling/annulations of quinazolones with alkynes for access to fused polycyclic heteroarenes under mild conditions. Org. Biomol. Chem. 2014, 12, 758–764. 10.1039/c3ob41955j. [DOI] [PubMed] [Google Scholar]
- a Shuklov I.; Börner A.; Dubrovina N. Fluorinated alcohols as solvents, cosolvents and additives in homogeneous catalysis. Synthesis 2007, 2925–2943. 10.1055/s-2007-983902. [DOI] [Google Scholar]; b Bonnet-Delpon D.; Bégué J.-P.; Crousse B. Fluorinated alcohols: a new medium for selective and clean reaction. Synlett 2004, 18–29. 10.1055/s-2003-44973. [DOI] [Google Scholar]
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