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. 2006 Aug 22;11(8):615–626. doi: 10.3390/11080615

Synthesis of Conformationally Constrained Aryl- or Heteroaryl-piperazinyl Derivatives of Selected Imides as 5-HT1A Receptor Ligands

Jerzy Kossakowski 1,*, Mariola Krawiecka 1, Bożena Kuran 1
PMCID: PMC6148633  PMID: 17971734

Abstract

The preparation of a number of cyclic imide 5-HT1A receptor ligand derivatives has been described. Their structures were conformationally constrained by introducing rigid linkers containing unsaturated bonds or aromatic benzene rings. These compounds are expected to possess anxiolytic and antidepressant activity.

Keywords: Conformational constraints; cis- and trans-2-butene derivatives; 1,2-bismethylbenzene derivatives; imides; 5-HT1A receptor ligands

Introduction

Many compounds containing the arylpiperazine moiety posses high affinity and selectivity for 5-HT1A receptors (e.g. buspirone, gepirone, tandospirone, NAN-190, BMY7378) and have been applied as anxiolytic and antidepressant drugs [1,2,3,4]. Recent studies show that constraining the chain in the ligands can have a significant influence on their affinities towards serotonin receptors [5,6].

We have previously described the synthesis of select aryl- or heteroarylpiperazinylimide derivatives with constrained alkyl chains. This work is a continuation of our previous studies in search for compounds with anxiolytic and antidepressant activity among a group of long-chain arylpiperazine ligands [7,8,9,10,11,12,13,14,15].

Results and Discussion

The synthesis of the target compounds is presented in Scheme 1. The starting materials for the synthesis of the new compounds were a selection of imides A-E, the linkers cis- and trans-1,4-dichloro-2-butene and 1,2-bis(chloromethyl)benzene and the amines 1-(2-methoxyphenyl)piperazine and 1-(2-pyrimidyl)piperazine (Figure 1). Imides A-D, F-G were obtained from the Diels-Alder reactions of maleimide and an appropriate diene and imide E was a commercially available reagent. They were reacted in acetonitrile or acetone in the presence of anhydrous K2CO3 and KI with the linkers cis-, or trans-1,4-dichloro-2-butene and 1,2-bis-(chloromethyl)benzene. Finally, the resulting N‑substituted imides were used to alkylate 1-(2-methoxyphenyl)piperazine or 1-(2-pyrimidinyl)-piperazine in acetone, again in the presence of anhydrous K2CO3 and KI, to give new derivatives I-XXXIV (Table 1).

Scheme 1.

Scheme 1

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The syntheses of the target compounds I-XXXIV

Figure 1.

Figure 1

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The components used in the reactions.

Table 1.

Numbering of derivatives obtained in the described reactions.

imide linker graphic file with name molecules-11-00615-i001.jpg graphic file with name molecules-11-00615-i002.jpg
A i I II
ii III IV
iii V VI
B i VII VIII
ii IX X
iii XI XII
C i XIII XIV
ii XV XVI
iii XVII XVIII
D i XIX XX
ii XXI XXII
iii XXIII XXIV
E iii XXV XXVI
F i XXVII XXVIII
ii XXIX
iii XXX XXXI
G iiii XXXII
XXXIII XXXIV
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The structures of the all compounds obtained were confirmed by 1H-NMR spectra, elemental analysis and/or ESI MS.

Conclusions

In continuation of our research on cyclic imides with potential anxiolytic and antidepressive activity we have obtained thirty four new compounds belonging to the long-chain arylpiperazine ligand class. From the chemical and pharmacological point of view, these compounds are the basis for further research in the field of the potential drugs derived from cyclic imides.

Experimental

General

Melting points were determined in a capillary on an Electrothermal 9100 apparatus and are given uncorrected. 1H-NMR spectra were recorded in DMSO-d6 on a Bruker AVANCE DMX400 spectrometer operating at 400 MHz. The chemical shift values are expressed in ppm (parts per million) relatively to tetramethylsilane used as an internal standard and coupling constants J are given in Hz. The ESI MS were recorded on a Mariner Perspective–Biosystem instrument. Column chromatography was done using 0.05-0.2 mm Kieselgel (70-325 mesh ASTM, Merck). Reactions were monitored by TLC on 0.2 mm thick Kieselgel G plates with 254 nm fluorescent indicator (Merck), eluted with 9.8:0.2 or 9.5:0.5 chloroform-methanol. The imides A, C, D, F, G were obtained according to the methods described previously [13,14,15]. The imide E was commercially available (Aldrich).

Synthesis of 1,7-diacetoxy-4-azatricyclo[5.2.2.02,6]undecan-3,5-dione (B)

A mixture of 2-cyclohexene-1,4-dione (0.01 mol), maleimide (0.01 mol) and a catalytic amount of p-toluenesulphonic acid (PTSA) was refluxed for 2h in isopropenyl acetate (30 mL). The boiling mixture was filtered and the solvent was evaporated. The residue was crystallized from ethyl acetate; m.p. 246°C; 1H-NMR δ (ppm): 11.26 (s, 1H, NH), 6.17 (s, 2H, C8-H, C9-H), 3.86 (s, 2H, C2-H, C6‑H), 2.35 (m, 2H, C10-H), 2.06 (s, 6H, C1-OAc, C7-OAc), 1.6 (d, C11-H, 3J=4.8); Anal. Calc. for C14H15NO6: 57.34 % C, 6.16 % H, 4.78% N; found: 57.43 % C, 5.21 % H, 4.80 % N.

General method for the preparation of the target compounds I-XXXIV: Synthesis of N- chloroalkenyl derivatives of the imides

The appropriate imide (0.01 mol) was dissolved in acetonitrile (30 mL, for C-E) or acetone (30 mL, for A-B, F-G), then anhydrous K2CO3 (0.01 mol), a catalytic amount of KI and the appropriate linker - cis-, or trans-1,4-dichloro-2-butene or 1,2-bis(chloromethyl)benzene (0.01 mol) - were added. The mixture was stirred at room temperature for 12-24 h. When the reaction was complete, as indicated by TLC, the mixture was filtered and the solvent was evaporated. The residue was purified by flash chromatography (eluent: chloroform-methanol 100:0.2).

Synthesis of aryl- and heteroarylpiperazinyl N-substituted imide derivatives

1-(2-Methoxyphenyl)piperazine or 1-(2-pyrimidinyl)piperazine (0.01 mol) were added to a mixture of N-chloroalkenylimide (0.01 mol), powdered anhydrous K2CO3 (0.01 mol), and a catalytic amount of KI in acetone (30 mL) The reaction mixture was stirred at a room temperature for 24 h. After the reaction completion the inorganic residue was filtered off and the solvent was evaporated. The crude compound obtained was purified by flash chromatography (eluents: chloroform or chloroform-methanol 100:0.2). All new derivatives were converted into their corresponding hydrochlorides with ethereal HCl and recrystallized from methanol.

4-{(2E)-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-en-1-yl}-1-methoxy-4-azatricyclo[5.2.2.02,6]undec-8-ene-3,5-dione (I): m.p. 166 °C; 1H-NMR δ (ppm): 10.63 (s, 1H, NH+), 7.04-6.09 (m, 4H, Harom.), 6.07-6.01 (m, 2H, C8-H, C9-H), 5.76-5.74 (m, 1H, C2’-H), 5.60-5.54 (m, 1H, C3’-H), 4.05 (d, 2H, C4’-H, 3J=8.0), 3.95 (m, 2H, C1’-H), 3.79 (s, 3H, OCH3), 3.52-3.45 (m, 4H, C5’-H, C7’-H), 3.36 (s, 3H, C1‑OCH3), 3.27-3.29 (m, 1H, C2-H), 3.21-3.16 (m, 2H, C6’-H), 3.08-3.06 (m, 1H, C6-H), 3.02-2.92 (m, 3H, C7-H, C8’-H), 1.94-1.87 (m, 1H, C10-H), 1.74-1.71 (m, 1H, C10-H), 1.41-1.34 (m,1H, C11‑H), 1.23-1.20 (m, 1H, C11-H); Anal. Calc. for C26H33N3O4·HCl·2H2O: 59.59 % C, 7.31 % H, 8.01% N; found: 59.01 % C, 6.86 % H, 7.97 % N.

4-{(2Z)-[4-pirimidylpiperazin-1-yl]but-2-en-1-yl}-1-methoxy-4-azatricyclo[5.2.2.02,6]undec-8-ene-3,5-dione (II): m.p. 230 °C; 1H-NMR δ (ppm): 11.53 (s, 1H, NH+), 8.45 (d, 2H, 3J=4.0, C9’-H, C11’-H), 6.77 (t, 1H, 3J=4.4, 4.8, C10’-H), 6.08-6.00 (m, 2H, C8-H, C9-H), 5.80-5.75 (m, 1H, C2’-H), 5.59-5.55 (m, 1H, C3’-H), 4.72 (d, 2H, 3J=14, C4’-H), 4.01 (d, 2H, 3J=6.8, C1’-H), 3.89 (m, 2H, C5’‑H, C7’-H), 3.47-3.38 (m, 4H, C5’-H, C6’-H, C7’-H), 3.35 (s, 3H, C1-OCH3), 3.28-3.26 (m, 1H, C2-H), 3.07-3.01 (m, 1H, C6-H, C8’-H), 2.91 (m, 1H, C7-H), 1.91-1.87 (m, 1H, C10-H), 1.73-1.68 (m, 1H, C10-H), 1.40-1.33 (m, 1H, C11-H), 1.22-1.16 (m, 1H, C11-H); Anal. Calc. for C23H29N5O3· HCl·2H2O: 60.06 % C, 6.57 % H, 15.23% N; found: 59.98 % C, 6.63 % H, 15.07 % N.

4-{(2Z)-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-en-1-yl}-1-methoxy-4-azatricyclo[5.2.2.02,6]undec-8-ene-3,5-dione (III): m.p. 153 °C; 1H-NMR δ (ppm): 11.21 (s, 1H, NH+), 7.03-6.88 (m, 4H, Harom.), 6.18-6.12 (m, 2H, C8-H, C9-H), 5.86-5.79 (m, 1H, C2’-H), 5.65-5.57 (m, 1H, C3’-H), 3.94-3.93 (d, 2H, 3J=4.4, C4’-H), 3.78 (s, 3H, OCH3), 3.73 (m, 2H, C5’-H, C7’-H), 3.48 (m, 2H, C1’-H), 3.36 (s, 3H, C1‑OCH3), 3.33-3.28 (m, 4H, C5’-H, C6’-H, C7’-H), 3.09-3.07 (m, 4H, C2-H, C6-H, C8’-H), 3.00 (m, 1H, C7-H), 1.92-1.97 (m, 1H, C10-H), 1.74-1.69 (m, 1H, C10-H), 1.41-1.35 (m, 1H, C11-H), 1.24-1.18 (m, 1H, C11-H); ESI MS: m/z = 451.56:452.2 (100%).

4-{(2E)-[4-pirimidylpiperazin-1-yl]but-2-en-1-yl}-1-methoxy-4-azatricyclo[5.2.2.02,6]undec-8-ene-3,5-dione (IV): m.p.147-152 °C; 1H-NMR δ (ppm): 11.29 (s, 1H, NH+), 8.45-8.44 (d, 2H, 3J=4.4, C9’‑H, C11’-H), 6.76 (t, 1H, 3J=4.8, C10’-H), 6.15-6.09 (m, 2H, C8-H, C9-H), 5.82-5.76 (m, 1H, C2’‑H), 5.64-5.56 (m, 1H, C3’-H), 4.68 (d, 2H, 3J=14, C4’-H), 3.93-3.92 (m, 2H, C1’-H), 3.70 (m, 2H, C5’-H, C7’-H), 3.40-3.27 (m, 7H, C1-OCH3, C5’-H, C6’-H, C7’-H), 3.29-3.27 (m, 1H, C2-H), 3.08-3.06 (m, 1H, C6-H), 2.92-2.88 (m, 2H, C7-H, C8’-H), 1.93-1.87 (m, 1H, C10-H), 1.74-1.69 (m, 1H, C10-H), 1.41-1.35 (m, 1H, C11-H), 1.24-1.17 (m, 1H, C11-H); ESI MS: m/z = 423.51:424.4 (100%), 446.6 (5%).

4-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]methylbenzyl}-1-methoxy-4-azatricyclo[5.2.2.02,6]undec-8-ene-3,5-dione (V): m.p.189 °C (for HCl); 1H-NMR (free base) δ (ppm): 7.17 (m, 4H, C7’-H, C8’-H, C9’-H, C10’-H), 7.01-6.96 (m, 1H, C11’-H), 6.91-6.90 (m, 2H, C12’-H, C13’-H), 6.84 (m, 1H, C14’‑H), 6.18-6.08 (m, 1H, C8-H), 6.05-6.02 (m, 1H, C9-H), 4.88-4.79 (m, 4H, C1’-H, C2’-H), 3.85 (s, 3H, OCH3), 3.69 (m, 2H, C3’-H, C5’-H), 3.50 (s, 3H, C1-OCH3), 3.14-2.88 (m, 5H, C2-H, C6-H, C7-H, C3’-H, C5’-H), 2.61 (m, 4H, C4’-H, C6’-H), 1.85-1.68 (m, 2H, C10-H), 1.55-1.47 (m, 2H, C11-H); Anal. Calc. for C30H35N3O4·6H2O (free base): 59.12 % C, 5.78 % H, 6.89% N; found: 59.35 % C, 5.44 % H, 6.45 % N; ESI MS: m/z = 501.2:502.2 (100%).

4-[2-(4-pirimidylpiperazin-1-yl)methylbenzyl]-1-methoxy-4-azatricyclo[5.2.2.02,6]undec-8-ene-3,5-dione (VI): m.p. 163 °C; 1H-NMR δ (ppm): 10.32 (s, 1H, NH+), 8.01 (d, 2H, 3J=4.4, C7’-H, C10’‑H), 7.26-7.25 (d, 1H, 3J=7.2, C11’-H), 7.00-6.92 (m, 2H, C8’-H, C9’-H), 6.70-6.68 (d, 1H, 3J=7.2, C13’‑H), 6.32 (t, 1H, 3J=4.8, C12’-H), 5.61-5.53 (m, 2H, C8-H, C9-H), 4.30-4.24 (m, 4H, C1’‑H, C2’‑H), 4.08 (m, 2H, C3’-H, C5’-H), 3.17 (m, 3H, C1-OCH3, C3’-H, C5’-H), 2.99-2.91 (m, 4H, C4’‑H, C6’-H), 2.77-2.69 (m, 3H, C2-H, C6-H, C7-H), 1.49-1.45 (m, 1H, C10-H), 1.31-1.25 (m, 1H, C10-H), 0.97-0.91 (m, 1H, C11-H), 0.79-0.74 (m, 1H, C11-H); Anal. Calc. for C27H31N5O3· HCl·½H2O: 63.58 % C, 6.32 % H, 13.73% N; found: 62.27 % C, 6.43 % H, 13.41 % N; ESI MS: m/z = 473.5:474.2 (100%).

4-{(2E)-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-en-1-yl}-3,5-dioxo-4-azatricyclo[5.2.2.02,6]undec-8-ene-1,7-diyl diacetate (VII): m.p. 206 °C; 1H-NMR δ (ppm): 10.88 (s, 1H, NH+), 7.00-6.90 (m, 4H, Harom.), 6.14 (s, 2H, C8-H, C9-H), 5.78 (m, 1H, C2’-H), 5.60 (m, 1H, C3’-H), 4.08 (d, 2H, 2J=8.0, C4’‑H), 3.96 (m, 4H, C2-H, C6-H, C5’-H, C6’-H), 3.79 (s, 3H, OCH3), 3.49 (m, 4H, C1’-H, C5’-H, C7’‑H), 3.18 (m, 2H, C6’-H), 3.02 (m, 2H, C8’-H), 2.41 (d, 1H, 2J=5.6, C10-H), 2.07 (m, 6H, C1‑OAc, C7-OAc), 1.72 (d, 1H, 2J=6.8, C11-H); ESI MS: m/z = 537.6:532.5 (100%).

4-{(2Z)-[4-pirimidylpiperazin-1-yl]but-2-en-1-yl}-3,5-dioxo-4-azatricyclo[5.2.2.02,6]undec-8-ene-1,7-diyl diacetate (VIII): m.p. 215 °C; 1H-NMR δ (ppm): 11.83 (s, 1H, NH+), 8.46-8.45 (m, 2H, C9’-H, C11’‑H), 6.79-6.77 (m, 1H, C10’-H), 6.13 (s, 2H, C8-H, C9-H), 5.89-5.79 (m, 1H, C2’-H), 5.64-5.5 (m, 1H, C3’-H), 4.72-4.69 (m, 2H, C5’-H, C7’-H), 4.03-4.02 (m, 2H, C4’-H), 3.96 (m, 2H, C2-H, C6‑H), 3.89 (m, 2H, C1’-H), 3.46-4.34 (m, 4H, C6’-H, C8’-H), 3.04-3.01 (m, 2H, C5’-H, C7’-H), 2.4-2.39 (m, 2H, C10-H), 2.07 (m, 6H, C1-OAc, C7-OAc), 1.73-1.71 (m, 2H, C11-H); ESI MS: m/z = 509.5:510.2 (100%).

4-{(2Z)-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-en-1-yl}-3,5-dioxo-4-azatricyclo[5.2.2.02,6]undec-8-ene-1,7-diyl diacetate (IX): m.p. 168 °C; 1H-NMR δ (ppm): 11.48 (s, 1H, NH+), 7.04-6.88 (m, 4H, Harom.), 6.26 (s, 2H, C8-H, C9-H), 5.86-5.80 (m, 1H, C2’-H), 5.66-5.59 (m, 1H, C3’-H), 3.97 (s, 2H, C2-H, C6-H), 3.94 (m, 2H, C4’-H), 3.78 (s, 3H, OCH3), 3.72 (m, 2H, C1’-H), 3.49-3.47 (m, 2H, C5’‑H, C7’-H), 3.38-3.33 (m, 2H, C5’-H, C7’-H), 3.15-3.05 (m, 4H, C6’-H, C8’-H), 2.40 (d, 2H, 3J=6.4, C10-H), 2.07 (s, 6H, C1-OAc, C7-OAc), 2.72 (d, 2H, 3J=6.8, C11-H); ESI MS: m/z = 537.3:538.2 (100%).

4-{(2E)-[4-pirimidylpiperazin-1-yl]but-2-en-1-yl}-3,5-dioxo-4-azatricyclo[5.2.2.02,6]undec-8-ene-1,7-diyl diacetate (X): m.p. 198 °C; 1H-NMR δ (ppm): 11.80 (s, 1H, NH+), 8.45-8.44 (d, 2H, 3J=4.4, C9’‑H, C11’-H), 6.77 (t, 1H, 3J=4.8, C10’-H), 6.24 (s, 2H, C8-H, C9-H), 5.83-5.76 (m, 1H, C2’-H), 5.65-5.58 (m, 1H, C3’-H), 3.97 (s, 2H, C2-H, C6-H), 4.67 (d, 2H, 3J=14, C4’-H), 3.96 (s, 2H, C2-H, C6-H), 3.98-3.82 (m, 2H, C1’-H), 3.70 (m, 2H, C5’-H, C7’-H), 3.45-3.34 (m, 4H, C6’-H, C8’-H), 2.94-2.87 (m, 2H, C5’-H, C7’-H), 2.39 (d, 2H, 3J=6.8, C10-H), 2.07 (s, 6H, C1-OAc, C7-OAc), 2.72 (d, 2H, 3J=6.8, C11-H); ESI MS: m/z = 509.5:510.2 (100%), 532.2 (15%).

4-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]methylbenzyl}-3,5-dioxo-4-azatricyclo[5.2.2.02,6]undec-8-ene-1,7-diyl diacetate (XI): m.p. 215 °C; 1H-NMR δ (ppm): 7.58-7.56 (m, 1H, C7’-H), 7.46-7.38 (m, 1H, C10’-H), 7.22-7.19 (m, 1H, C8’-H), 7.13-7.11 (m, 1H, C9’-H), 7.03-6.95 (m, 2H, C11’-H, C14’‑H), 6.92-6.87 (m, 2H, C12’, C13’-H), 6.15-6.12 (m, 2H, C8-H, C9-H), 4.70-4.68 (m, 1H, C2’-H), 4.55-4.48 (m, 2H, C1’-H), 4.07 (s, 1H, C2-H), 4.01 (s, 1H, C6-H), 3.77 (s, 3H, OCH3), 3.55-3.33 (m, 6H, C3’-H, C4’-H, C5’-H, C6’-H), 2.96-2.90 (m, 1H, C2’-H), 2.49-2.39 (m, 2H, C10-H), 2.05 (s, 6H, C1-OAc, C7-OAc), 1.73-1.71 (m, 2H, C11-H); ESI MS: m/z = 587.6:588.3 (100%).

4-[2-(4-pirimidylpiperazin-1-yl)methylbenzyl]-3,5-dioxo-4-azatricyclo[5.2.2.02,6]undec-8-ene-1,7-diyl diacetate (XII): m.p. 197 °C; 1H-NMR δ (ppm): 11.22 (s, 1H, NH+), 8.45 (m, 2H, C11’-H, C13’-H), 7.76-7.74 (m, 1H, C10’-H), 7.44-7.35 (m, 2H, C8’-H, C9’-H), 7.14-7.12 (m, 1H, C7’-H), 6.76 (t, 1H, 3J= 4.8, C12’), 6.12 (s, 2H, C8-H, C9-H), 4.70-4.68 (m, 4H, C3’-H, C5’-H), 4.49-4.48 (m, 2H, C2’-H), 4.06-4.04 (m, 2H, C2-H, C6-H), 3.51-3.35 (m, 4H, C4’-H, C6’-H), 3.20-3.16 (m, 2H, C1’-H), 2.42-2.41 (m, 2H, C10-H), 2.06 (s, 6H, C1-OAc, C7-OAc), 1.73-1.71 (m, 2H, C11-H); ESI MS: m/z = 559.6:560.4 (100%).

2-{(2Z)-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-en-1-yl}-4,7-dichloro-4,7-ethano-3a,4,9,9a-tetra-hydro-1H-dibenzo[fi]isoindole-1,3-(2H)-dione (XIII): m.p. 175 °C (for HCl); 1H-NMR (free base) δ (ppm): 7.77 (m, 2H, C8-H, C11-H), 7.57 (m, 2H, C12-H, C15-H), 7.43 (m, 2H, C9-H, C10-H), 7.37 (m, 2H, C13-H, C14-H), 6.90-6.85 (m, 4H, C9’-H-C12’-H), 5.25-5.23 (m, 1H, C2’-H), 4.34-4.32 (m, 1H, C3’-H), 3.75 (s, 3H, OCH3), 3.68 (d, 2H, 3J=6.4, C1’-H), 3.60 (s, 2H, C2-H, C6-H), 2.89 (m, 6H, C4’-H, C6’-H, C8’-H), 2.40 (m, 4H, C5’-H, C7’-H); Anal. Calc. for C33H31Cl2N3O3·11/2H2O (free base): 64.40 % C, 5.55 % H, 6.83% N; found: 68.62 % C, 5.35 % H, 6.75 % N; ESI MS: m/z = 588.5:589.2 (100%).

2-{(2Z)-[4-pirimidylpiperazin-1-yl]but-2-en-1-yl}-4,7-dichloro-4,7-ethano-3a,4,9,9a-tetrahydro-1H-dibenzo[fi]isoindole-1,3-(2H)-dione (XIV): m.p. 188 °C; 1H-NMR (DMSO-d6) δ (ppm): 11.73 (s, 1H, NH+), 8.46 (d, 2H, 3J=4.4, C9’-H, C11’-H), 7.82-7.80 (m, 2H, C8-H, C11-H), 7.61-7.59 (m, 2H, C12‑H, C15-H), 7.47-7.46 (m, 2H, C9-H, C10-H), 7.42-7.40 (m, 2H, C13-H, C14-H), 6.78 (t, 1H, 3J=4.4, 4.8, C10’-H), 5.59-5.53 (m, 1H, C2’-H), 4.72-4.69 (m, 2H, C4’-H), 4.63-4.57 (m, 1H, C3’-H), 3.77-3.76 (m, 4H, C5’-H, C7’-H), 3.68-3.64 (s, 2H, C2-H, C6-H), 3.46-3.36 (m, 4H, C6’-H, C8’-H), 2.98-2.95 (m, 2H, C1’-H); ESI MS: m/z = 559.5:560.1 (100%), 562.1 (65%).

2-{(2E)-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-en-1-yl}-4,7-dichloro-4,7-ethano-3a,4,9,9a-tetra-hydro-1H-dibenzo[fi]isoindole-1,3-(2H)-dione (XV): m.p. 240 °C; 1H-NMR δ (ppm): 10.40 (s, 1H, NH+), 7.83-7.81 (m, 2H, C11-H, C12-H), 7.65-7.63 (m, 2H, C8-H, C15-H), 7.48-7.45 (m, 4H, C9-H, C10-H, C13-H, C14-H), 7.05-6.90 (m, 4H, C9’-H-C12’-H), 5.28 (m, 1H, C3’-H), 5.02-4.95 (m, 2H, C4’-H), 4.61-4.57 (m, 1H, C2’-H), 3.80 (s, 3H, OCH3), 3.71 (d, 2H, 3J= 5.6, C1’-H), 3.66 (s, 2H, C2‑H, C6-H), 3.55-3.52 (m, 2H, C5’-H, C7’-H), 3.35-3.33 (m, 2H, C5’-H, C7’-H), 3.09-2.96 (m, 4H, C6’-H, C8’-H); ESI MS: m/z = 588.5:589.2 (100%).

2-{(2E)-[4-pirimidylpiperazin-1-yl]but-2-en-1-yl}-4,7-dichloro-4,7-ethano-3a,4,9,9a-tetrahydro-1H-dibenzo[fi]isoindole-1,3-(2H)-dione (XVI): m.p. 210 °C; 1H-NMR δ (ppm): 11.48 (s,1H, NH+), 8.47 (d, 2H, 3J=4.4, C9’-H, C11’-H), 7.81-7.80 (m, 2H, C8-H, C15-H), 7.62-7.61 (m, 2H, C9-H, C10‑H), 7.47-7.44 (m, 4H, C13-H, C14-H, C11-H, C-12H), 6.78 (t, 1H, 3J=4.4, C10’-H), 5.35-5.27 (m, 1H, C3’-H), 4.97-4.92 (m, 2H, C2’-H), 4.74-4.71 (m, 1H, C4’-H), 3.70-3.65 (s, 4H, C1’-H, C2-H, C6-H), 3.49 (m, 2H, C5’-H, C7’-H), 3.43-3.32 (m, 4H, C6’-H, C8’-H), 2.91-2.88 (m, 2H, C5’-H, C7’‑H); ESI MS: m/z = 559.5:560.2 (100%).

2-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]methylbenzyl}-4,7-dichloro-4,7-ethano-3a,4,9,9a-tetrahydro-1H-dibenzo[fi]isoindole-1,3-(2H)-dione (XVII): m.p. 225 °C; 1H-NMR δ (ppm): 7.83-7.80 (m, 2H, C11-H, C12-H), 7.67-7.65 (m, 2H, C8-H, C15-H), 7.52-7.50 (m, 2H, C10-H, C9-H), 7.48-7.46 (m, 2H, C13-H, C14-H), 7.13-7.10 (m, 2H, C8’-H, C9’-H), 6.91-6.84 (m, 5H, C7’-H, C10’-H, C11’-H C12’-H, C14’-H), 4.99-4.97 (m, 1H, C13’-H), 4.60 (s, 2H, C2’-H), 3.75 (s, 3H, OCH3), 3.72 (m, 2H, C1’-H), 3.46 (m, 2H, C2-H, C6-H), 2.87 (m, 4H, C3’-H, C5’-H), 2.33 (m, 4H, C4’-H, C6’-H); Anal. Calc. for C37H33Cl2N3O3·2HCl·5H2O: 58.35 % C, 5.65 % H, 5.52% N; found: 58.61 % C, 5.68 % H, 5.10 % N; ESI MS: m/z = 637.5:638.1 (100%), 640.2 (60%).

2-[2-(4-pirimidylpiperazin-1-yl)methylbenzyl]-4,7-dichloro-4,7-ethano-3a,4,9,9a-tetrahydro-1H-dibenzo[fi]isoindole-1,3-(2H)-dione (XVIII): m.p. 273 °C; 1H-NMR (for HCl) δ (ppm): 8.33-8.30 (m, C11’-H, C13’-H), 7.81-7.79 (m, 2H, C11-H, C8-H), 7.65-7.63 (m, 2H, C12-H, C15-H), 7.49-7.44 (m, 4H, C10-H, C9-H, C13-H, C14-H), 7.13-7.07 (m, 2H, C8’-H, C9’-H), 6.86-6.83 (m, 1H, C10’-H), 6.61-6.58 (m, 1H, C7’-H), 5.03-5.01 (d, 1H, C12’-H), 4.60 (m, 2H, C2’-H), 3.71 (m, 2H, C1’-H), 3.63 (m, 4H, C3’-H, C6’-H), 3.44 (m, 2H, C2-H, C6-H), 2.33 (m, 4H, C4’-H, C5’-H); Anal. Calc. for C34H29Cl2N5O2·21/2H2O (free base): 62.29 % C, 4.45 % H, 10.68% N; found: 62.72 % C, 4.79 % H, 10.76 % N; ESI MS: m/z = 609.5:610.1 (100%), 612.1 (60%).

2-{(2Z)-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-en-1-yl}-4-trifluoroacetyl-4,7-ethano-3a,4,9,9a-tetrahydro-1H-dibenzo[fi]isoindole-1,3-(2H)-dione (XIX): m.p. 168 °C; 1H-NMR δ (ppm): 11.39 (s, 1H, NH+), 7.66-7.58 (m, 2H, C8-H, C11-H), 7.34-7.26 (m, 5H, C10-H, C12-H, C13-H, C14-H, C15‑H), 7.05-6.89 (m, 5H, C9-H, C9’-H, C10’-H, C11’-H, C12’-H), 5.56-5.50 (m, 1H, C2’-H), 4.92 (m, 1H, C7-H), 4.50-4.45 (m, 1H, C6-H), 4.16-4.14 (m, 1H, C3’-H), 3.80 (s, 3H, OCH3), 3.76 (m, 3H, C2-H, C5’-H, C7’-H ), 3.49-3.48 (m, 2H, C4’-H), 3.40-3.32 (m, 2H, C5’-H, C7’-H), 3.16-3.03 (m, 4H, C1’-H, C6’-H), 2.08 (m, 2H, C8’-H); ESI MS: m/z = 615.6:616.3 (100%).

2-{(2Z)-[4-pirimidylpiperazin-1-yl]but-2-en-1-yl}-4-trifluoroacetyl-4,7-ethano-3a,4,9,9a-tetrahydro-1H-dibenzo[fi]isoindole-1,3-(2H)-dione (XX): m.p. 163 °C; 1H-NMR δ (ppm): 8.33-8.31 (m, 2H, C9’‑H, C11’-H), 7.64 (m, 1H, C11-H), 7.47-7.45 (m, 1H, C12-H), 7.31-7.21 (m, 5H, C8-H, C9-H, C10-H,C13-H, C14-H), 7.05-7.03 (m, 1H, C15-H), 6.51 (m, 1H, C10’-H), 5.44 (m, 1H, C2’-H), 4.78 (m, 1H, C7-H), 4.51 (m, 1H, C3’-H), 3.98 (d, 1H, 3J=8.4, C2-H), 3.83 (m, 4H, C5’-H, C7’-H), 3.72-3.65 (m, 2H, C4’-H), 3.30-3.28 (m, 1H, C6-H), 3.04 (m, 2H, C1’-H), 2.48 (m, 4H, C6’-H, C8’-H); ESI MS: m/z = 587.5:588.2 (100%), 610.2 (2%).

2-{(2E)-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-en-1-yl}-4-trifluoroacetyl-4,7-ethano-3a,4,9,9a-tetrahydro-1H-dibenzo[fi]isoindole-1,3-(2H)-dione (XXI): m.p. 180 °C; 1H-NMR δ (ppm): 11.47 (s, 1H, NH+), 7.59 (m, 2H, C11-H, C12-H), 7.34-7.26 (m, 5H, C8-H, C10-H, C13-H, C14-H, C15-H), 7.05-6.91 (m, 5H, C9-H, C9’-H, C10’-H, C11’-H, C12’-H), 5.56-5.48 (m, 1H, C3’-H), 4.93 (s, 1H, C7-H), 4.82-4.75 (m, 1H, C2’-H), 4.15 (d, 1H, 3J=8.4, C2-H), 3.80 (s, 3H, -OCH3), 3.63 (m, 2H, C4’-H), 3.52-3.49 (m, 5H, C6-H, C5’-H, C7’-H), 3.38-3.33 (m, 2H, C1’-H), 3.07 (m, 4H, C6’-H, C8’-H); ESI MS: m/z = 615.6:616.3 (100%).

2-{(2E)-[4-pirimidylpiperazin-1-yl]but-2-en-1-yl}-4-trifluoroacetyl-4,7-ethano-3a,4,9,9a-tetrahydro-1H-dibenzo[fi]isoindole-1,3-(2H)-dione (XXII): m.p. 204 °C; 1H-NMR δ (ppm): 11.67 (s, 1H, NH+), 8.45 (d, 2H, 3J=4.4, C9’-H, C11’-H) 7.66-7.57 (m, 2H, C11-H, C12-H), 7.36-7.28 (m, 5H, C8-H, C9‑H, C10-H, C13-H, C14-H), 6.97-6.95 (m, 1H, C15-H), 5.52-5.48 (m, 1H, C3’-H), 4.92 (s, 1H, C7‑H), 4.79-4.69 (m, 1H, C2’-H), 4.14 (d, 1H, 3J=8, C2-H), 3.62-3.61 (m, 2H, C4’-H), 3.49-3.35 (m, 9H, C6-H, C5’-H, C7’-H), 2.92-2.89 (m, 2H, C1’-H); ESI MS: m/z = 587.5:588.2 (100%), 610.2 (2%).

2-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]methylbenzyl}-4-trifluoroacetyl-4,7-ethano-3a,4,9,9a-tetra-hydro-1H-dibenzo[fi]isoindole-1,3-(2H)-dione (XXIII): m.p. 190 °C; 1H-NMR δ (ppm): 10.67 (s, 1H, NH+), 7.65-7.59 (m, 3H, C8-H, C11-H, C12-H), 7.36-7.25 (m, 5H, C9-H, C10-H, C13-H, C14-H, C15-H), 7.20-7.14 (m, 3H, C7’-H, C10’-H, C14-H), 7.02-6.95 (m, 3H, C8’-H, C9’-H, C11’-H), 6.91 (m, 2H, C12’-H, C14’-H), 5.93-5.91 (m, 1H, C13’-H), 4.94-4.93 (m, 1H, C7-H), 4.49 (m, 2H, C2’-H), 4.38-4.37 (m, 2H, C1’-H), 4.28-4.26 (m, 1H, C2-H), 4.12 (m, 4H, C3’-H, C5’-H), 3.79 (s, 3H, OCH3), 3.58-3.56 (m, 1H, C6-H), 3.47-3.44 (m, 2H, C4’-H), 3.08 (m, 2H, C6’-H); ESI MS: m/z = 665.7:666.2 (100%).

2-[2-(4-pirimidylpiperazin-1-yl)methylbenzyl]-4-trifluoroacetyl-4,7-ethano-3a,4,9,9a-tetrahydro-1H-dibenzo[fi]isoindole-1,3-(2H)-dione (XXIV): m.p. 196 °C; 1H-NMR δ (ppm): 11.16 (s, 1H, NH+), 8.45-8.43 (m, 2H, C11’-H, C13’-H), 7.65-7.63 (m, 2H, C11-H, C12-H), 7.58-7.56 (m, 1H, C15-H), 7.35-7.25 (m, 4H, C9-H, C10-H, C13-H, C14-H), 7.20-7.13 (m, 3H, C7’-H, C9’-H, C10’-H), 6.96-6.94 (m, 1H, C8-H), 6.77 (m, 1H, C12’-H), 5.91-5.89 (d, 1H, 3J=7.6, C8’-H), 4.93 (m, 1H, C7-H), 4.70-4.66 (m, 4H, C3’-H, C5’-H), 4.53-4.49 (m, 2H, C2’-H), 4.33-4.32 (m, 2H, C1’-H), 4.26-4.24 (m, 1H, C2-H), 3.56-3.54 (m, 1H, C6-H), 3.35-3.31 (m, 2H, C4’-H), 3.16-3.11 (m, 2H, C6’-H); Anal. Calc. for C36H30F3N5O3·HCl·4H2O: 57.95 % C, 5.27 % H, 9.39% N; found: 58.47 % C, 5.12 % H, 9.34 % N.

2-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]methylbenzyl}-3a,6-dihydro-1H-benzo[de]isoquinoline-1,3-(2H)-dione (XXV): m.p. 239 °C; 1H-NMR δ (ppm): 10.32 (s, 1H, NH+), 8.54 (t, 4H, 3J=9.6, 8.0, C6‑H, C8-H, C10-H, C12-H), 7.91 (t, 2H, 3J=7.6, C7-H, C11-H), 7.74 (d, 1H, 3J=6.4, C10’-H), 7.38-7.32 (m, 2H, C8’-H, C9’-H), 7.26 (m, 1H, C7’-H), 7.05-6.98 (m, 4H, C12’-H, C13’-H, C14’-H, C15’-H), 5.49 (m, 2H, C2’-H), 4.76 (m, 2H, C1’-H), 3.81 (s, 3H, OCH3), 3.56-3.46 (m, 6H, C3’-H, C4’-H, C5’-H), 3.15-3.09 (m, 2H, C6’-H); Anal. Calc. for C31H29N3O3·HCl·4H2O: 61.84 % C, 6.64 % H, 6.98% N; found: 61.43 % C, 5.81 % H, 6.74 % N.

2-[2-(4-pirimidylpiperazin-1-yl)methylbenzyl]-3a,6-dihydro-1H-benzo[de]isoquinoline-1,3(2H)-dione (XXVI): m.p. 258 °C; 1H-NMR δ (ppm): 10.48 (s, 1H, NH+), 8.54 (t, 4H, 3J=8.0, C6-H, C8-H, C10-H, C12-H), 8.46 (d, 2H, 3J=4.8, C7-H, C11-H), 7.91 (t, 1H, 3J=7.6, C8’-H, C9’-H), 7.72 (m, 1H, C7’-H), 7.35 (m, 2H, C11’-H, C13’-H), 7.25 (m, 1H, C10’-H), 6.78 (t, 1H, 3J=4.8, C12’-H), 5.45 (s, 2H, C2’‑H), 4.80 (m, 2H, C1’-H), 4.70 (m, 2H, C3’-H, C5’-H), 3.56-3.53 (m, 2H, C3’-H, C5’-H), 3.47-3.31 (m, 4H, C4’-H, C6’-H); Anal. Calc. for C28H25N5O2·HCl·H2O: 64.61 % C, 5.38 % H, 13.47% N; found: 64.34 % C, 5.32 % H, 13.50 % N.

4-{(2E)-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-en-1-yl}-7,11-dimethyl-3,5-dioxo-4-azatricyclo [5.2.2.02,6]undec-8-en-1-yl acetate (XXVII): m.p. 144 °C; 1H-NMR δ (ppm): 7.04-6.91 (m, 2H, C9’‑H, C12’-H), 5.99-5.94 (m, 2H, C10’-H, C11’-H), 5.72 (s, 1H, C9-H), 5.63-5.60 (m, 1H, C3‘-H), 4.15-4.13 (m, 2H, C4‘-H), 4.06-3.94 (m, 3H, C1’-H, C2’-H), 3.81-3.79 (m, 8H, C2-H, C5’-H, C7’-H, OCH3), 3.40-3.35 (m, 4H, C6’-H, C8’-H), 3.20-3.18 (m, 1H, C6-H), 2.61-2.54 (m, 2H, C7-H, C10-H), 2.04 (m, 4H, C1-OAc, C11-H), 1.53 (s, 3H, C8-CH3), 0.98-0.94 (m, 1H, C10-H), 0.79 (d, 3H, 3J=16.8, C11-CH3); ESI MS: m/z = 507.6:508.3 (100%).

4-{(2Z)-[4-pirimidylpiperazin-1-yl]but-2-en-1-yl}-7,11-dimethyl-3,5-dioxo-4-azatricyclo[5.2.2.02,6] undec-8-en-1-yl acetate (XXVIII): m.p. 190 °C; 1H-NMR δ (ppm): 11.79 (s, 1H, NH+), 8.45 (d, 2H, 3J=4.8, C9’-H, C11’-H), 6.77 (t, 1H, 3J=4.8, C10‘-H), 5.70 (s, 1H, C9-H), 5.55-5.49 (m, 1H, C2‘-H), 4.72-4.68 (m, 2H, C4‘-H), 4.02-4.01 (m, 2H, C5’-H, C7’-H), 3.90-3.88 (m, 2H, C4’-H), 3.78-3.76 (m, 1H, C3’-H), 3.47-3.41 (m, 4H, C6’-H, C8’-H), 3.17-3.14 (m, 1H, C6-H), 3.03 (m, 2H, C5’-H, C6’-H), 2.59-2.52 (m, 2H, C7-H, C10-H), 2.08-2.03 (m, 5H, C1-OAc, C2-H, C11-H), 1.65 (s, 3H, C8-CH3), 0.97-0.93 (m, 1H, C10-H), 0.79 (d, 3H, 3J=6.4, C11-CH3); ESI MS: m/z = 479.5:480.3 (100%).

4-{(2Z)-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-en-1-yl}-7,11-dimethyl-3,5-dioxo-4-azatricyclo [5.2.2.02,6]undec-8-en-1-yl acetate (XXIX): m.p. 149°C; 1H-NMR δ (ppm): 11.50 (s, 1H, NH+), 7.02-6.90 (m, 4H, Harom.), 5.89-5.60 (m, 3H, C9-H, C2’-H, C3‘-H), 3.94 (m, 2H, C4’-H), 3.78 (s, 3H, OCH3), 3.73 (m, 2H, C5‘-H), 3.48 (m, 2H, C7’-H), 3.40-3.35 (m, 3H, C2-H, C1’-H), 3.17 (m, 1H, C6-H), 3.07 (m, 4H, C6’-H, C8’-H), 2.60-2.55 (m, 2H, C7-H, C10-H), 2.04 (s, 4H, C1-OAc, C11-H), 1.71 (s, 3H, C8-CH3), 0.98-0.95 (m, 1H, C10-H), 0.81 (d, 3H, 3J=6.4, C11-CH3); ESI MS: m/z = 507.6:508.4 (100%).

4-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]methylbenzyl}-7,11-dimethyl-3,5-dioxo-4-azatricyclo [5.2.2.02,6]undec-8-en-1-yl acetate (XXX): m.p. 153 °C; 1H-NMR δ (ppm): 10.95 (s, 1H, NH+), 7.77-7.76 (m, 1H, C10’-H), 7.44-7.35 (m, 2H, C8’-H, C9’-H), 7.09-7.07 (m, 1H, C7’-H), 7.03-6.91 (m, 4H, C11’-H, C12’-H, C13’-H, C14’-H), 5.67 (s, 1H, C9-H), 4.78-4.68 (m, 2H, C2’-H), 4.59-4.50 (m, 2H, C1’-H), 3.88-3.86 (m, 1H, C2-H), 3.78 (s, 3H, OCH3), 3.49-3.35 (m, 6H, C3’-H, C4’-H, C5’-H), 3.25-3.23 (m, 1H, C6-H), 3.18-3.13 (m, 2H, C6’-H), 2.59-2.54 (m, 2H, C7-H, C10-H), 2.04 (m, 4H, C1‑OAc, C11-H), 1.53 (s, 3H, C8-CH3), 0.98-0.94 (m, 1H, C10-H), 0.79 (d, 3H, 3J=6.4, C11- CH3); ESI MS: m/z = 557.6:558.3 (100%).

4-[2-(4-pirimidylpiperazin-1-yl)methylbenzyl]-7,11-dimethyl-3,5-dioxo-4-azatricyclo[5.2.2.02,6]undec-8-en-1-yl acetate (XXXI): m.p. 173°C; 1H-NMR δ (ppm): 8.43 (d, 2H, 3J=4.0, C11’-H, C13’-H), 7.67 (d, 1H, 3J=5.6, C10’-H), 7.46-7.34 (m, 2H, C8’-H, C9’-H), 7.05 (d, 1H, 3J=8.0, C7’-H), 6.76 (t, 1H, 3J=4.0, C12’-H), 5.67 (s, 1H, C9-H), 4.72-4.62 (m,4H, C3’-H, C5’-H), 4.56-4.42 (m, 2H, C2’-H), 3.84 (d, 1H, 3J=8.0, C2-H), 3.40-3.33 (m, 6H, C1’-H, C4’-H, C6’-H), 3.23-3.20 (m, 2H, C6-H, C7-H), 2.55 (m, 1H, C10-H), 2.01 (m, 4H, C1-OAc, C11-H), 1.50 (s, 3H, C8-CH3), 0.95-0.92 (m, 1H, C10‑H), 0.77 (d, 3H, 3J=8.2, C11- CH3); Anal. Calc. for C30H35N5O4·HCl·31/2H2O: 57.23 % C, 6.83 % H, 11.13% N; found: 57.44 % C, 6.41 % H, 11.08 % N.

4-{(2E)-[4-(2-methoxyphenyl)piperazin-1-yl]but-2-en-1-yl}-1,11-dimethyl-4-azatricyclo[5.2.2.02,6] un-decane-3,5,8-trione (XXXII): m.p. 175 °C; 1H-NMR δ (ppm): 10.94 (s, 1H, NH+), 7.03-6.90 (m, 4H, Harom.), 5.84-5.78 (m, 1H, C2’-H), 5.64-5.58 (m, 1H, C3’-H), 4.16-4.07 (m, 2H, C5’-H, C7’-H), 3.96 (m, 2H, C4’-H), 3.79 (s, 3H, OCH3), 3.49-3.43 (m, 4H, C6’-H, C8’-H), 3.37-3.34 (m, 1H, C6-H), 3.21-3.16 (m, 2H, C5’-H, C7’-H), 3.05-2.99 (m, 2H, C1’-H), 2.84-2.82 (m, 1H, C2-H), 2.44 (m, 1H, C7-H), 2.19 (m, 1H, C11-H), 2.09-2.05 (m, 1H, C9-H), 1.94-1.88 (m, 1H, C10-H), 1.77-1.71 (m, 1H, C9-H), 1.99 (s, 3H, C1-CH3), 1.09-1.01 (m, 1H, C10-H), 0.85 (d, 3H, 3J=7.2, C11-CH3); ESI MS: m/z = 465.5:466.2 (100%).

4-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]methylbenzyl}-1,11-dimethyl-4-azatricyclo[5.2.2.02,6]-undecane-3,5,8-trione (XXXIII): m.p. 186 °C; 1H-NMR δ (ppm): 7.70 (m, 1H, C7’-H), 7.46-7.43 (m, 2H, C8’-H, C9’-H), 7.10 (m, 1H, C10’-H), 7.03-6.82 (m, 4H, C11’-H, C12’-H, C13’-H, C14’-H), 4.82-4.64 (m, 2H, C5-H, C3’-H), 4.61 (s, 2H, C2’-H), 3.86 (s, 3H, OCH3), 3.50-3.33 (m, 7H, C6-H, C3’-H, C4’-H, C5’-H, C6’-H), 3.11-3.05 (m, 2H, C1’-H), 2.87 (d, 1H, 3J=9.2, C2-H), 2.49-2.45 (m, 1H, C7-H), 2.17 (m, 1H, C11-H), 2.00 (d, 1H, 3J=20, C9-H), 1.89 (t, 1H, 3J=12, C10-H), 1.60 (d, 1H, 3J=20, C9-H), 1.14 (s, 3H, C1-CH3), 1.05-0.97 (m, 1H, C10-H), 0.84 (d, 3H, 3J=8, C11-CH3); Anal. Calc. for C31H37N3O4 ·HCl·31/2H2O: 60.49 % C, 7.32 % H, 6.83% N; found: 60.98 % C, 7.08 % H, 6.31 % N.

4-[2-(4-pirimidylpiperazin-1-yl)methylbenzyl]-1,11-dimethyl-4-azatricyclo[5.2.2.02,6]undecane-3,5,8-trione (XXXIV): m.p. 176 °C; 1H-NMR δ (ppm): 8.43 (d, 2H, 3J=4.6, C11’-H, C13’-H), 8.29-8.12 (m, 1H, C10’-H), 7.35 (m, 2H, C8’-H, C9’-H), 7.09 (m, 1H, C7’-H), 6.75 (t, 1H, 3J=4.8, C12’-H), 4.78-4.57 (m, 4H, C3’-H, C5’-H,), 4.53 (s, 2H, C2’-H), 3.44-3.33 (m, 4H, C4’-H, C6’-H), 3.23-3.14 (m, 3H, C6-H, C1’-H), 2.87 (d, 1H, 3J=8, C2-H), 2.43 (m, 1H, C7-H), 2.18 (m, 1H, C11-H), 2.10-1.95 (m, 1H, C9-H), 1.93-1.81 (m, 1H, C10-H), 1.60-1.57 (m, 1H, C9-H), 1.13 (s, 3H, C1-CH3), 1.05-0.97 (m, 1H, C10-H), 0.84 (d, 3H, 3J=8, C11-CH3); Anal. Calc. for C28H33N5O3·HCl·31/2H2O: 57.24 % C, 6.98 % H, 11.93% N; found: 57.23 % C, 6.39 % H, 11.89 % N.

Footnotes

Sample availability: Samples of the compounds are available from authors.

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