1,4-Dimethyl-2-phenyl-6,7-dihydro-1H-pyrazolo­[4,3-b]pyridine-3,5(2H,4H)-dione

Abstract

The mean plane of the pyrazolone ring [maximum deviation = 0.054 (1) Å] of the title compound, C₁₄H₁₅N₃O₂, is oriented at a dihedral angle of 36.05 (7)° with respect to the phenyl ring. The methyl group is slightly disposed [distance = 0.864 (2) Å] out of the mean plane of the pyrazolone ring to which it is attached.

Related literature

For the biological activity of pyrazolone derivates (e.g. dipyrone), see: Pierre et al. (2007 ▶). For general methods of clevage of N-Cbz protected amines see: Greene & Wuts (1999 ▶). For conversion of N-Cbz-protected amines into N-t-Boc-protected amines, see: Sakaitani et al. (1988 ▶).

Experimental

Crystal data

• C₁₄H₁₅N₃O₂

• M _r = 257.29

• Monoclinic,

• a = 8.9721 (7) Å

• b = 21.7653 (19) Å

• c = 7.3725 (5) Å

• β = 120.214 (5)°

• V = 1244.12 (17) ų

• Z = 4

• Mo Kα radiation

• μ = 0.10 mm⁻¹

• T = 193 K

• 0.45 × 0.17 × 0.16 mm

Data collection

• Stoe IPDS 2T diffractometer

• 4103 measured reflections

• 1623 independent reflections

• 1541 reflections with I > 2σ(I)

• R _int = 0.036

Refinement

• R[F ² > 2σ(F ²)] = 0.027

• wR(F ²) = 0.071

• S = 1.04

• 1623 reflections

• 174 parameters

• 2 restraints

• H-atom parameters constrained

• Δρ_max = 0.18 e Å⁻³

• Δρ_min = −0.14 e Å⁻³

Data collection: X-AREA (Stoe, 2010 ▶); cell refinement: X-AREA; data reduction: X-RED (Stoe, 2010 ▶); program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: PLATON.

Supplementary Material

Supplementary material file. DOI: 10.1107/S1600536811036233/bt5636Isup3.cdx

Supplementary material file. DOI: 10.1107/S1600536811036233/bt5636Isup4.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

supplementary crystallographic information

Comment

Pyrazolone derivates are widely known as potent analgesic drugs (Pierre et al., 2007). By transforming the protection group from a N-Cbz group into a N-t-Boc group in an one pot synthesis (Sakaitani et al., 1988) with the structure 3-(4-((benzyloxycarbonyl)(methyl)amino)-2-methyl-5-oxo-1-phenyl-2,5-dihydro-1H-pyrazol-3-yl)propanoic acid, a ringclosure to sixmembered ring was formed. For further investigation, we omitted the step of conversion and performed a direct clevage reaction (Greene & Wuts, 1999) leading to the title compound.

The pyrazolone ring of the anellated ringsystem is oriented at a dihedral angle of 36.05 (7)° with respect to the phenyl ring. The methyl group (C17) shows a distance of 0.864 (2) Å to the least square plane of the pyrazolone ring system.

Experimental

The compound was prepared by palladium catalzyed cleaverage of a N-Cbz protected amine (Greene & Wuts, 1999). 3-(4-((Benzyloxycarbonyl)(methyl)amino)-2-methyl-5-oxo-1-phenyl-2,5-dihydro-1H-pyrazol-3-yl)propanoic acid (0.74 g, 1.81 mmol) and palladium on activated carbon (10%, 0.19 g, 0.18 mmol) were dissolved in 40 ml ethyl acetate under a hydrogen atmosphere (1 atm). The mixture was stirred for 12 h with regular TLC monitoring, then filtered and concentrated. The resulting residue was purified by flash chromatography (SiO₂, ethyl acetate/isopropyl alcohol 1:1). Crystals of the title compound were obtained by slow evaporation of ethanol at room temperature.

Refinement

In the absence of anomalous scatterers, Friedel pairs were merged. Hydrogen atoms were placed at calculated positions with C—H = 0.95 Å (aromatic) or 0.98–0.99 Å (sp³ C-atom). All H atoms were refined in the riding-model approximation with isotropic displacement parameters set at 1.2–1.5 times of the U_eq of the parent atom.

Figures

Fig. 1.

View of compound I. Displacement ellipsoids are drawn at the 50% probability level.

Crystal data

C14H15N3O2	F(000) = 544
Mr = 257.29	Dx = 1.374 Mg m−3
Monoclinic, Cc	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C -2yc	Cell parameters from 6605 reflections
a = 8.9721 (7) Å	θ = 2.8–29.3°
b = 21.7653 (19) Å	µ = 0.10 mm−1
c = 7.3725 (5) Å	T = 193 K
β = 120.214 (5)°	Plate, colourless
V = 1244.12 (17) Å3	0.45 × 0.17 × 0.16 mm
Z = 4

Data collection

Stoe IPDS 2T diffractometer	1541 reflections with I > 2σ(I)
Radiation source: sealed Tube	Rint = 0.036
graphite	θmax = 28.9°, θmin = 2.8°
Detector resolution: 6.67 pixels mm-1	h = −12→12
rotation method scans	k = −29→25
4103 measured reflections	l = −9→10
1623 independent reflections

Refinement

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.027	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.071	H-atom parameters constrained
S = 1.04	w = 1/[σ2(Fo2) + (0.0454P)2 + 0.1582P] where P = (Fo2 + 2Fc2)/3
1623 reflections	(Δ/σ)max < 0.001
174 parameters	Δρmax = 0.18 e Å−3
2 restraints	Δρmin = −0.14 e Å−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
N1	0.35428 (16)	0.22736 (6)	0.2232 (2)	0.0248 (3)
C2	0.31867 (18)	0.27099 (7)	0.3359 (2)	0.0250 (3)
C3	0.36758 (18)	0.32872 (6)	0.2826 (2)	0.0241 (3)
C4	0.43857 (18)	0.31670 (7)	0.1635 (2)	0.0240 (3)
N5	0.44486 (16)	0.25431 (6)	0.1332 (2)	0.0239 (2)
C6	0.37458 (19)	0.16362 (7)	0.2688 (2)	0.0245 (3)
C7	0.2491 (2)	0.13330 (7)	0.2930 (3)	0.0305 (3)
H7	0.1517	0.1550	0.2782	0.037*
C8	0.2679 (3)	0.07098 (8)	0.3392 (3)	0.0386 (4)
H8	0.1846	0.0503	0.3602	0.046*
C9	0.4070 (3)	0.03872 (8)	0.3550 (3)	0.0420 (4)
H9	0.4181	−0.0040	0.3852	0.050*
C10	0.5303 (2)	0.06878 (8)	0.3266 (3)	0.0373 (4)
H10	0.6246	0.0465	0.3351	0.045*
C11	0.5156 (2)	0.13149 (8)	0.2858 (3)	0.0301 (3)
H11	0.6012	0.1524	0.2696	0.036*
O12	0.26349 (16)	0.25874 (6)	0.45386 (19)	0.0330 (3)
N13	0.35152 (17)	0.38830 (6)	0.3448 (2)	0.0291 (3)
C14	0.4310 (2)	0.43628 (7)	0.3067 (3)	0.0311 (3)
C15	0.5584 (2)	0.41980 (8)	0.2363 (3)	0.0328 (3)
H15A	0.6707	0.4100	0.3621	0.039*
H15B	0.5757	0.4563	0.1690	0.039*
C16	0.5053 (2)	0.36558 (7)	0.0828 (3)	0.0290 (3)
H16A	0.4149	0.3785	−0.0594	0.035*
H16B	0.6059	0.3503	0.0748	0.035*
C17	0.3917 (2)	0.23369 (8)	−0.0807 (2)	0.0291 (3)
H17A	0.2717	0.2458	−0.1759	0.044*
H17B	0.4018	0.1889	−0.0821	0.044*
H17C	0.4662	0.2527	−0.1267	0.044*
C18	0.2290 (3)	0.40112 (8)	0.4156 (3)	0.0394 (4)
H18A	0.2698	0.4362	0.5119	0.059*
H18B	0.2191	0.3650	0.4883	0.059*
H18C	0.1159	0.4107	0.2942	0.059*
O19	0.4061 (2)	0.48961 (6)	0.3370 (2)	0.0423 (3)

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
N1	0.0286 (6)	0.0233 (6)	0.0300 (6)	−0.0013 (4)	0.0203 (5)	0.0012 (5)
C2	0.0246 (6)	0.0261 (7)	0.0255 (6)	0.0001 (5)	0.0136 (5)	0.0008 (5)
C3	0.0255 (6)	0.0227 (6)	0.0252 (7)	−0.0010 (5)	0.0136 (5)	0.0018 (5)
C4	0.0232 (6)	0.0254 (7)	0.0241 (6)	−0.0015 (5)	0.0124 (5)	0.0023 (5)
N5	0.0259 (5)	0.0252 (6)	0.0259 (6)	−0.0023 (4)	0.0171 (5)	0.0005 (5)
C6	0.0281 (6)	0.0216 (6)	0.0244 (6)	−0.0030 (5)	0.0136 (5)	−0.0020 (5)
C7	0.0339 (8)	0.0282 (8)	0.0337 (8)	−0.0062 (6)	0.0203 (6)	−0.0040 (6)
C8	0.0523 (10)	0.0289 (8)	0.0423 (10)	−0.0126 (7)	0.0295 (8)	−0.0047 (7)
C9	0.0576 (11)	0.0207 (7)	0.0462 (10)	−0.0034 (7)	0.0249 (8)	0.0007 (7)
C10	0.0389 (8)	0.0272 (8)	0.0416 (10)	0.0044 (6)	0.0173 (7)	−0.0011 (6)
C11	0.0272 (7)	0.0269 (7)	0.0333 (8)	−0.0022 (5)	0.0130 (6)	−0.0022 (6)
O12	0.0435 (6)	0.0324 (6)	0.0363 (6)	−0.0002 (5)	0.0299 (5)	0.0015 (5)
N13	0.0343 (6)	0.0240 (6)	0.0316 (6)	0.0003 (5)	0.0185 (5)	−0.0012 (5)
C14	0.0378 (8)	0.0243 (7)	0.0265 (7)	−0.0023 (6)	0.0127 (6)	0.0009 (6)
C15	0.0341 (7)	0.0276 (7)	0.0346 (8)	−0.0066 (6)	0.0157 (6)	0.0040 (6)
C16	0.0305 (7)	0.0293 (7)	0.0297 (7)	−0.0030 (5)	0.0170 (6)	0.0053 (6)
C17	0.0277 (7)	0.0353 (8)	0.0270 (7)	−0.0014 (6)	0.0159 (6)	−0.0038 (6)
C18	0.0490 (10)	0.0332 (8)	0.0491 (10)	0.0044 (7)	0.0343 (9)	−0.0036 (7)
O19	0.0596 (8)	0.0229 (6)	0.0438 (7)	−0.0010 (5)	0.0255 (6)	−0.0012 (5)

Geometric parameters (Å, °)

N1—C2	1.4009 (19)	C10—C11	1.390 (2)
N1—N5	1.4098 (16)	C10—H10	0.9500
N1—C6	1.4173 (18)	C11—H11	0.9500
C2—O12	1.2269 (18)	N13—C14	1.371 (2)
C2—C3	1.449 (2)	N13—C18	1.462 (2)
C3—C4	1.344 (2)	C14—O19	1.224 (2)
C3—N13	1.4069 (19)	C14—C15	1.517 (3)
C4—N5	1.3820 (19)	C15—C16	1.536 (2)
C4—C16	1.485 (2)	C15—H15A	0.9900
N5—C17	1.4691 (19)	C15—H15B	0.9900
C6—C7	1.392 (2)	C16—H16A	0.9900
C6—C11	1.395 (2)	C16—H16B	0.9900
C7—C8	1.388 (2)	C17—H17A	0.9800
C7—H7	0.9500	C17—H17B	0.9800
C8—C9	1.385 (3)	C17—H17C	0.9800
C8—H8	0.9500	C18—H18A	0.9800
C9—C10	1.389 (3)	C18—H18B	0.9800
C9—H9	0.9500	C18—H18C	0.9800
C2—N1—N5	110.78 (12)	C6—C11—H11	120.2
C2—N1—C6	124.29 (12)	C14—N13—C3	119.08 (13)
N5—N1—C6	118.88 (12)	C14—N13—C18	119.34 (14)
O12—C2—N1	124.53 (14)	C3—N13—C18	120.76 (13)
O12—C2—C3	131.78 (14)	O19—C14—N13	121.55 (16)
N1—C2—C3	103.65 (12)	O19—C14—C15	121.68 (15)
C4—C3—N13	123.53 (13)	N13—C14—C15	116.69 (14)
C4—C3—C2	108.44 (13)	C14—C15—C16	115.22 (13)
N13—C3—C2	128.01 (13)	C14—C15—H15A	108.5
C3—C4—N5	111.62 (12)	C16—C15—H15A	108.5
C3—C4—C16	122.80 (14)	C14—C15—H15B	108.5
N5—C4—C16	125.56 (13)	C16—C15—H15B	108.5
C4—N5—N1	104.62 (11)	H15A—C15—H15B	107.5
C4—N5—C17	117.15 (13)	C4—C16—C15	107.06 (13)
N1—N5—C17	115.18 (12)	C4—C16—H16A	110.3
C7—C6—C11	120.43 (14)	C15—C16—H16A	110.3
C7—C6—N1	118.59 (14)	C4—C16—H16B	110.3
C11—C6—N1	120.98 (13)	C15—C16—H16B	110.3
C8—C7—C6	119.23 (16)	H16A—C16—H16B	108.6
C8—C7—H7	120.4	N5—C17—H17A	109.5
C6—C7—H7	120.4	N5—C17—H17B	109.5
C9—C8—C7	120.61 (16)	H17A—C17—H17B	109.5
C9—C8—H8	119.7	N5—C17—H17C	109.5
C7—C8—H8	119.7	H17A—C17—H17C	109.5
C8—C9—C10	120.07 (16)	H17B—C17—H17C	109.5
C8—C9—H9	120.0	N13—C18—H18A	109.5
C10—C9—H9	120.0	N13—C18—H18B	109.5
C9—C10—C11	119.95 (16)	H18A—C18—H18B	109.5
C9—C10—H10	120.0	N13—C18—H18C	109.5
C11—C10—H10	120.0	H18A—C18—H18C	109.5
C10—C11—C6	119.67 (15)	H18B—C18—H18C	109.5
C10—C11—H11	120.2
N5—N1—C2—O12	−169.21 (15)	N5—N1—C6—C11	19.2 (2)
C6—N1—C2—O12	−17.1 (2)	C11—C6—C7—C8	1.5 (2)
N5—N1—C2—C3	8.97 (15)	N1—C6—C7—C8	−179.53 (16)
C6—N1—C2—C3	161.12 (13)	C6—C7—C8—C9	−1.9 (3)
O12—C2—C3—C4	173.11 (17)	C7—C8—C9—C10	0.7 (3)
N1—C2—C3—C4	−4.88 (15)	C8—C9—C10—C11	1.1 (3)
O12—C2—C3—N13	−5.2 (3)	C9—C10—C11—C6	−1.5 (3)
N1—C2—C3—N13	176.85 (14)	C7—C6—C11—C10	0.2 (2)
N13—C3—C4—N5	177.41 (13)	N1—C6—C11—C10	−178.76 (16)
C2—C3—C4—N5	−0.95 (17)	C4—C3—N13—C14	−8.7 (2)
N13—C3—C4—C16	−0.9 (2)	C2—C3—N13—C14	169.31 (14)
C2—C3—C4—C16	−179.27 (13)	C4—C3—N13—C18	160.80 (16)
C3—C4—N5—N1	6.36 (17)	C2—C3—N13—C18	−21.2 (2)
C16—C4—N5—N1	−175.38 (13)	C3—N13—C14—O19	172.06 (16)
C3—C4—N5—C17	135.25 (13)	C18—N13—C14—O19	2.4 (2)
C16—C4—N5—C17	−46.5 (2)	C3—N13—C14—C15	−11.1 (2)
C2—N1—N5—C4	−9.63 (16)	C18—N13—C14—C15	179.24 (16)
C6—N1—N5—C4	−163.47 (12)	O19—C14—C15—C16	−143.95 (16)
C2—N1—N5—C17	−139.69 (13)	N13—C14—C15—C16	39.2 (2)
C6—N1—N5—C17	66.46 (18)	C3—C4—C16—C15	26.93 (19)
C2—N1—C6—C7	50.1 (2)	N5—C4—C16—C15	−151.14 (15)
N5—N1—C6—C7	−159.82 (13)	C14—C15—C16—C4	−44.36 (18)
C2—N1—C6—C11	−130.91 (15)