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

Weisser, M.; Schollmeyer, D.; Laufer, S.

doi:10.1107/S1600536811036233

organic compounds

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ISSN: 2056-9890

Volume 67| Part 10| October 2011| Page o2586

https://doi.org/10.1107/S1600536811036233

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

Marc Weisser,^a Dieter Schollmeyer ^b and Stefan Laufer ^a ^*

^aEberhard-Karls-University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany, and ^bUniversity Mainz, Institut of Organic Chemistry, Duesbergweg 10-14, 55099 Mainz, Germany
^*Correspondence e-mail: stefan.laufer@uni-tuebingen.de

(Received 5 September 2011; accepted 5 September 2011; online 14 September 2011)

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, C c
a = 8.9721 (7) Å
b = 21.7653 (19) Å
c = 7.3725 (5) Å
β = 120.214 (5)°
V = 1244.12 (17) Å³
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[F² > 2σ(F²)] = 0.027
wR(F²) = 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.

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536811036233/bt5636sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536811036233/bt5636Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S1600536811036233/bt5636Isup3.cdx

Supporting information file. DOI: https://doi.org/10.1107/S1600536811036233/bt5636Isup4.cml

checkCIF report

Comment top

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.

Related literature top

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 top

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.

Structure description top

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).

Computing details top

Data collection: X-AREA (Stoe, 2010); cell refinement: X-AREA (Stoe, 2010); 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 (Spek, 2009).

Figures top

Fig. 1. View of compound I. Displacement ellipsoids are drawn at the 50% probability level.

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

Crystal data top

C₁₄H₁₅N₃O₂	F(000) = 544
M_r = 257.29	D_x = 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 top

Stoe IPDS 2T diffractometer	1541 reflections with I > 2σ(I)
Radiation source: sealed Tube	R_int = 0.036
Graphite monochromator	θ_max = 28.9°, θ_min = 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 top

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(F_o²) + (0.0454P)² + 0.1582P] where P = (F_o² + 2F_c²)/3
1623 reflections	(Δ/σ)_max < 0.001
174 parameters	Δρ_max = 0.18 e Å⁻³
2 restraints	Δρ_min = −0.14 e Å⁻³

Crystal data top

C₁₄H₁₅N₃O₂	V = 1244.12 (17) Å³
M_r = 257.29	Z = 4
Monoclinic, Cc	Mo Kα radiation
a = 8.9721 (7) Å	µ = 0.10 mm⁻¹
b = 21.7653 (19) Å	T = 193 K
c = 7.3725 (5) Å	0.45 × 0.17 × 0.16 mm
β = 120.214 (5)°

Data collection top

Stoe IPDS 2T diffractometer	1541 reflections with I > 2σ(I)
4103 measured reflections	R_int = 0.036
1623 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.027	2 restraints
wR(F²) = 0.071	H-atom parameters constrained
S = 1.04	Δρ_max = 0.18 e Å⁻³
1623 reflections	Δρ_min = −0.14 e Å⁻³
174 parameters

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
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 (Å²) top

	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, º) top

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)

Experimental details

Crystal data
Chemical formula	C₁₄H₁₅N₃O₂
M_r	257.29
Crystal system, space group	Monoclinic, Cc
Temperature (K)	193
a, b, c (Å)	8.9721 (7), 21.7653 (19), 7.3725 (5)
β (°)	120.214 (5)
V (Å³)	1244.12 (17)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.45 × 0.17 × 0.16

Data collection
Diffractometer	Stoe IPDS 2T
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	4103, 1623, 1541
R_int	0.036
(sin θ/λ)_max (Å⁻¹)	0.680

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.027, 0.071, 1.04
No. of reflections	1623
No. of parameters	174
No. of restraints	2
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.18, −0.14

Computer programs: X-AREA (Stoe, 2010), X-RED (Stoe, 2010), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009).

References

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