tert-Butyl 3-amino-2-methyl-6,7-dihydro-2H-pyrazolo[4,3-c]pyridine-5(4H)-carboxyl­ate

Guo, X.; Bai, X.G.; Li, Y.L.; Wang, Y.C.

doi:10.1107/S1600536810013218

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 66| Part 5| May 2010| Page o1108

https://doi.org/10.1107/S1600536810013218

Open

access

tert-Butyl 3-amino-2-methyl-6,7-dihydro-2H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate

Xin Guo,^a Xiao Guang Bai,^a Yi Liang Li ^a and Yu Cheng Wang ^a ^*

^aInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing 100050, People's Republic of China
^*Correspondence e-mail: hongzhaoupr@yahoo.com

(Received 30 March 2010; accepted 9 April 2010; online 17 April 2010)

In the molecule of the title compound, C₁₂H₂₀N₄O₂, the dihydropiperidine ring assumes a half-chair conformation. In the crystal, cllassical N—H⋯O and N—H⋯N intermolecular hydrogen bonds link molecules into double chains along the a axis.

Related literature

For the synthesis and properties of related kinase inhibitors, see: Fancelli et al. (2005 ); Gadekar et al. (1968 ).

Experimental

Crystal data

C₁₂H₂₀N₄O₂
M_r = 252.32
Triclinic, $[P \overline 1]$
a = 6.3151 (13) Å
b = 9.3615 (19) Å
c = 11.215 (2) Å
α = 85.837 (4)°
β = 86.794 (4)°
γ = 87.733 (4)°
V = 659.8 (2) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 293 K
0.30 × 0.26 × 0.16 mm

Data collection

Rigaku, SCXmini diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005 ) T_min = 0.972, T_max = 0.985
6859 measured reflections
3008 independent reflections
1737 reflections with I > 2σ(I)
R_int = 0.052

Refinement

R[F² > 2σ(F²)] = 0.064
wR(F²) = 0.170
S = 1.01
3008 reflections
167 parameters
H-atom parameters constrained
Δρ_max = 0.28 e Å⁻³
Δρ_min = −0.36 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N4—H4A⋯O2ⁱ	0.86	2.32	3.093 (3)	149
N4—H4B⋯N2ⁱⁱ	0.86	2.57	3.420 (3)	172
Symmetry codes: (i) -x, -y+1, -z+1; (ii) x-1, y, z.

Data collection: CrystalClear (Rigaku, 2005); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL/PC (Sheldrick, 2008); software used to prepare material for publication: SHELXTL/PC.

Supporting information

Crystal structure: contains datablocks I, New_Global_Publ_Block. DOI: https://doi.org/10.1107/S1600536810013218/rz2434sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810013218/rz2434Isup2.hkl

checkCIF report

Comment top

In our ongoing project aimed at the develpment of potential anticancer kinase inhibitors (Fancelli et al., 2005; Gadekar et al., 1968), we have synthesized the title compound and report its crystal structure herein.

In the molecule of the title compound (Fig. 1), bond lengths and angles are within the expected range. The dehydropiperidine ring assumes a half-chair conformation, with atoms N1 and C1 displaced from the C2–C5 mean plane by -0.4493 (19) and 0.293 (3)° respectively. In the crystal packing (Fig. 2), classical N—H···O and N—H···N intermolecular hydrogen bonds (Table 1) link molecules into double chains along the a axis.

Related literature top

For the synthesis and properties of related kinase inhibitors, see: Fancelli et al. (2005); Gadekar et al. (1968).

Experimental top

A mixture of tert-butyl 3-cyano-4-oxopyrrolidine-1-carboxylate (2.1 g , 10.0 mmol) and methylhydrazine (0.46 g , 10.0 mol) was dissolved in ethanol (50 ml) and stirred at room temperature for 12 hours to give a white precipitate of the title compound. Colourless block crystals suitable for X-ray diffraction were obtained in 5 days by slow evaporation of a methanol solution (15 ml) of 100 mg of the crude product.

Structure description top

For the synthesis and properties of related kinase inhibitors, see: Fancelli et al. (2005); Gadekar et al. (1968).

Computing details top

Data collection: CrystalClear (Rigaku, 2005); cell refinement: CrystalClear (Rigaku, 2005); data reduction: CrystalClear (Rigaku, 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL/PC (Sheldrick, 2008); software used to prepare material for publication: SHELXTL/PC (Sheldrick, 2008).

Figures top

	Fig. 1. The molecular structure of the title compound, showing the atomic numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. Packing diagram of the title compound viewed along the b axis. Intermolecular hydrogen bonds are shown as dashed lines.

tert-Butyl 3-amino-2-methyl-6,7-dihydro-2H-pyrazolo[4,3-c]pyridine-5(4H)- carboxylate top

Crystal data top

C₁₂H₂₀N₄O₂	Z = 2
M_r = 252.32	F(000) = 272
Triclinic, P1	D_x = 1.270 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 6.3151 (13) Å	Cell parameters from 5123 reflections
b = 9.3615 (19) Å	θ = 3.2–27.5°
c = 11.215 (2) Å	µ = 0.09 mm⁻¹
α = 85.837 (4)°	T = 293 K
β = 86.794 (4)°	Block, colourless
γ = 87.733 (4)°	0.30 × 0.26 × 0.16 mm
V = 659.8 (2) Å³

Data collection top

Rigaku, SCXmini diffractometer	3008 independent reflections
Radiation source: fine-focus sealed tube	1737 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.052
Detector resolution: 13.6612 pixels mm^-1	θ_max = 27.5°, θ_min = 3.2°
ω scans	h = −8→8
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005)	k = −12→12
T_min = 0.972, T_max = 0.985	l = −14→14
6859 measured 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)] = 0.064	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.170	H-atom parameters constrained
S = 1.01	w = 1/[σ²(F_o²) + (0.081P)²] where P = (F_o² + 2F_c²)/3
3008 reflections	(Δ/σ)_max < 0.001
167 parameters	Δρ_max = 0.28 e Å⁻³
0 restraints	Δρ_min = −0.36 e Å⁻³

Crystal data top

C₁₂H₂₀N₄O₂	γ = 87.733 (4)°
M_r = 252.32	V = 659.8 (2) Å³
Triclinic, P1	Z = 2
a = 6.3151 (13) Å	Mo Kα radiation
b = 9.3615 (19) Å	µ = 0.09 mm⁻¹
c = 11.215 (2) Å	T = 293 K
α = 85.837 (4)°	0.30 × 0.26 × 0.16 mm
β = 86.794 (4)°

Data collection top

Rigaku, SCXmini diffractometer	3008 independent reflections
Absorption correction: multi-scan (CrystalClear; Rigaku, 2005)	1737 reflections with I > 2σ(I)
T_min = 0.972, T_max = 0.985	R_int = 0.052
6859 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.064	0 restraints
wR(F²) = 0.170	H-atom parameters constrained
S = 1.01	Δρ_max = 0.28 e Å⁻³
3008 reflections	Δρ_min = −0.36 e Å⁻³
167 parameters

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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
C1	0.3109 (4)	0.0363 (3)	0.6957 (2)	0.0386 (6)
H1A	0.2825	−0.0408	0.6462	0.046*
H1B	0.3436	−0.0061	0.7744	0.046*
C2	0.5027 (4)	0.1173 (3)	0.6406 (2)	0.0398 (6)
H2A	0.5619	0.1713	0.7007	0.048*
H2B	0.6113	0.0498	0.6125	0.048*
C3	0.4344 (4)	0.2180 (2)	0.5375 (2)	0.0331 (6)
C4	0.2211 (4)	0.2453 (3)	0.5144 (2)	0.0329 (5)
C5	0.0400 (4)	0.1836 (3)	0.59148 (19)	0.0385 (6)
H5A	−0.0710	0.2567	0.6030	0.046*
H5B	−0.0191	0.1057	0.5531	0.046*
C6	0.2214 (4)	0.3437 (3)	0.4173 (2)	0.0346 (6)
C7	0.5130 (4)	0.4687 (3)	0.2914 (2)	0.0479 (7)
H7A	0.3984	0.5194	0.2522	0.072*
H7B	0.5974	0.4162	0.2344	0.072*
H7C	0.5997	0.5358	0.3251	0.072*
C8	0.0740 (4)	0.2085 (3)	0.8027 (2)	0.0327 (5)
C9	0.1596 (4)	0.2266 (3)	1.0122 (2)	0.0371 (6)
C10	0.2487 (5)	0.3756 (3)	0.9930 (3)	0.0561 (8)
H10A	0.3934	0.3684	0.9622	0.084*
H10B	0.2431	0.4197	1.0679	0.084*
H10C	0.1660	0.4329	0.9369	0.084*
C11	−0.0678 (4)	0.2267 (3)	1.0624 (2)	0.0486 (7)
H11A	−0.1532	0.2919	1.0136	0.073*
H11B	−0.0739	0.2563	1.1427	0.073*
H11C	−0.1206	0.1319	1.0627	0.073*
C12	0.2991 (5)	0.1310 (3)	1.0927 (2)	0.0564 (8)
H12A	0.2457	0.0360	1.1008	0.085*
H12B	0.2984	0.1687	1.1701	0.085*
H12C	0.4416	0.1279	1.0580	0.085*
N1	0.1203 (3)	0.1310 (2)	0.70667 (17)	0.0353 (5)
N2	0.5648 (3)	0.2928 (2)	0.46032 (17)	0.0388 (5)
N3	0.4281 (3)	0.3700 (2)	0.38587 (17)	0.0386 (5)
N4	0.0539 (3)	0.4037 (2)	0.35407 (19)	0.0507 (6)
H4A	0.0781	0.4606	0.2915	0.061*
H4B	−0.0744	0.3840	0.3773	0.061*
O1	0.1814 (3)	0.15709 (17)	0.89818 (14)	0.0398 (4)
O2	−0.0535 (3)	0.31087 (19)	0.80320 (15)	0.0480 (5)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0362 (14)	0.0381 (14)	0.0400 (14)	0.0063 (11)	0.0030 (11)	−0.0011 (11)
C2	0.0327 (14)	0.0447 (15)	0.0402 (14)	0.0078 (11)	0.0001 (11)	0.0032 (12)
C3	0.0273 (12)	0.0387 (14)	0.0327 (12)	0.0038 (10)	−0.0009 (10)	−0.0015 (11)
C4	0.0268 (12)	0.0436 (14)	0.0285 (12)	0.0024 (10)	−0.0019 (9)	−0.0044 (10)
C5	0.0308 (13)	0.0529 (16)	0.0319 (13)	−0.0022 (11)	−0.0021 (10)	−0.0040 (12)
C6	0.0296 (13)	0.0445 (14)	0.0299 (12)	0.0033 (11)	−0.0042 (10)	−0.0053 (11)
C7	0.0437 (16)	0.0557 (17)	0.0420 (15)	−0.0021 (13)	0.0000 (12)	0.0110 (13)
C8	0.0271 (12)	0.0374 (13)	0.0323 (12)	−0.0002 (11)	0.0005 (10)	0.0037 (11)
C9	0.0413 (15)	0.0385 (14)	0.0312 (13)	−0.0011 (11)	−0.0013 (10)	−0.0018 (11)
C10	0.0587 (19)	0.0517 (18)	0.0591 (18)	−0.0151 (14)	−0.0054 (14)	−0.0026 (14)
C11	0.0493 (17)	0.0514 (17)	0.0440 (15)	−0.0054 (13)	0.0103 (13)	−0.0028 (13)
C12	0.065 (2)	0.0602 (19)	0.0440 (16)	0.0080 (15)	−0.0120 (14)	0.0000 (14)
N1	0.0302 (11)	0.0431 (12)	0.0317 (10)	0.0020 (9)	0.0024 (8)	−0.0015 (9)
N2	0.0274 (11)	0.0496 (13)	0.0376 (11)	0.0047 (9)	−0.0007 (9)	0.0052 (10)
N3	0.0292 (11)	0.0487 (13)	0.0360 (11)	0.0037 (9)	−0.0020 (9)	0.0067 (10)
N4	0.0365 (13)	0.0750 (17)	0.0386 (12)	0.0059 (11)	−0.0059 (10)	0.0092 (11)
O1	0.0475 (11)	0.0406 (10)	0.0307 (9)	0.0096 (8)	−0.0045 (7)	−0.0031 (7)
O2	0.0519 (12)	0.0496 (11)	0.0403 (10)	0.0201 (9)	−0.0040 (8)	0.0006 (8)

Geometric parameters (Å, º) top

C1—N1	1.471 (3)	C8—O2	1.227 (3)
C1—C2	1.532 (3)	C8—O1	1.349 (3)
C1—H1A	0.9700	C8—N1	1.354 (3)
C1—H1B	0.9700	C9—O1	1.474 (3)
C2—C3	1.509 (3)	C9—C11	1.513 (3)
C2—H2A	0.9700	C9—C12	1.516 (3)
C2—H2B	0.9700	C9—C10	1.521 (3)
C3—N2	1.340 (3)	C10—H10A	0.9600
C3—C4	1.396 (3)	C10—H10B	0.9600
C4—C6	1.375 (3)	C10—H10C	0.9600
C4—C5	1.502 (3)	C11—H11A	0.9600
C5—N1	1.460 (3)	C11—H11B	0.9600
C5—H5A	0.9700	C11—H11C	0.9600
C5—H5B	0.9700	C12—H12A	0.9600
C6—N3	1.360 (3)	C12—H12B	0.9600
C6—N4	1.384 (3)	C12—H12C	0.9600
C7—N3	1.448 (3)	N2—N3	1.382 (3)
C7—H7A	0.9600	N4—H4A	0.8600
C7—H7B	0.9600	N4—H4B	0.8600
C7—H7C	0.9600

N1—C1—C2	111.82 (19)	O1—C9—C11	111.03 (19)
N1—C1—H1A	109.3	O1—C9—C12	102.7 (2)
C2—C1—H1A	109.3	C11—C9—C12	110.1 (2)
N1—C1—H1B	109.3	O1—C9—C10	108.8 (2)
C2—C1—H1B	109.3	C11—C9—C10	113.5 (2)
H1A—C1—H1B	107.9	C12—C9—C10	110.2 (2)
C3—C2—C1	109.5 (2)	C9—C10—H10A	109.5
C3—C2—H2A	109.8	C9—C10—H10B	109.5
C1—C2—H2A	109.8	H10A—C10—H10B	109.5
C3—C2—H2B	109.8	C9—C10—H10C	109.5
C1—C2—H2B	109.8	H10A—C10—H10C	109.5
H2A—C2—H2B	108.2	H10B—C10—H10C	109.5
N2—C3—C4	112.4 (2)	C9—C11—H11A	109.5
N2—C3—C2	125.5 (2)	C9—C11—H11B	109.5
C4—C3—C2	122.1 (2)	H11A—C11—H11B	109.5
C6—C4—C3	105.4 (2)	C9—C11—H11C	109.5
C6—C4—C5	130.6 (2)	H11A—C11—H11C	109.5
C3—C4—C5	123.8 (2)	H11B—C11—H11C	109.5
N1—C5—C4	108.28 (18)	C9—C12—H12A	109.5
N1—C5—H5A	110.0	C9—C12—H12B	109.5
C4—C5—H5A	110.0	H12A—C12—H12B	109.5
N1—C5—H5B	110.0	C9—C12—H12C	109.5
C4—C5—H5B	110.0	H12A—C12—H12C	109.5
H5A—C5—H5B	108.4	H12B—C12—H12C	109.5
N3—C6—C4	106.7 (2)	C8—N1—C5	118.53 (19)
N3—C6—N4	123.2 (2)	C8—N1—C1	122.99 (19)
C4—C6—N4	129.9 (2)	C5—N1—C1	113.39 (19)
N3—C7—H7A	109.5	C3—N2—N3	103.51 (18)
N3—C7—H7B	109.5	C6—N3—N2	111.98 (19)
H7A—C7—H7B	109.5	C6—N3—C7	128.4 (2)
N3—C7—H7C	109.5	N2—N3—C7	119.56 (19)
H7A—C7—H7C	109.5	C6—N4—H4A	120.0
H7B—C7—H7C	109.5	C6—N4—H4B	120.0
O2—C8—O1	124.3 (2)	H4A—N4—H4B	120.0
O2—C8—N1	124.0 (2)	C8—O1—C9	121.18 (18)
O1—C8—N1	111.59 (19)

N1—C1—C2—C3	−42.3 (3)	C4—C5—N1—C8	104.8 (2)
C1—C2—C3—N2	−171.7 (2)	C4—C5—N1—C1	−50.8 (3)
C1—C2—C3—C4	9.9 (3)	C2—C1—N1—C8	−86.9 (3)
N2—C3—C4—C6	−0.3 (3)	C2—C1—N1—C5	67.4 (2)
C2—C3—C4—C6	178.3 (2)	C4—C3—N2—N3	0.0 (3)
N2—C3—C4—C5	−175.9 (2)	C2—C3—N2—N3	−178.6 (2)
C2—C3—C4—C5	2.8 (4)	C4—C6—N3—N2	−0.7 (3)
C6—C4—C5—N1	−157.6 (2)	N4—C6—N3—N2	−177.5 (2)
C3—C4—C5—N1	16.7 (3)	C4—C6—N3—C7	−178.1 (2)
C3—C4—C6—N3	0.6 (3)	N4—C6—N3—C7	5.1 (4)
C5—C4—C6—N3	175.7 (2)	C3—N2—N3—C6	0.4 (2)
C3—C4—C6—N4	177.1 (2)	C3—N2—N3—C7	178.1 (2)
C5—C4—C6—N4	−7.8 (4)	O2—C8—O1—C9	−2.9 (3)
O2—C8—N1—C5	9.7 (3)	N1—C8—O1—C9	178.62 (19)
O1—C8—N1—C5	−171.83 (18)	C11—C9—O1—C8	60.3 (3)
O2—C8—N1—C1	162.8 (2)	C12—C9—O1—C8	177.9 (2)
O1—C8—N1—C1	−18.7 (3)	C10—C9—O1—C8	−65.3 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N4—H4A···O2ⁱ	0.86	2.32	3.093 (3)	149
N4—H4B···N2ⁱⁱ	0.86	2.57	3.420 (3)	172

Symmetry codes: (i) −x, −y+1, −z+1; (ii) x−1, y, z.

Experimental details

Crystal data
Chemical formula	C₁₂H₂₀N₄O₂
M_r	252.32
Crystal system, space group	Triclinic, P1
Temperature (K)	293
a, b, c (Å)	6.3151 (13), 9.3615 (19), 11.215 (2)
α, β, γ (°)	85.837 (4), 86.794 (4), 87.733 (4)
V (Å³)	659.8 (2)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.30 × 0.26 × 0.16

Data collection
Diffractometer	Rigaku, SCXmini
Absorption correction	Multi-scan (CrystalClear; Rigaku, 2005)
T_min, T_max	0.972, 0.985
No. of measured, independent and observed [I > 2σ(I)] reflections	6859, 3008, 1737
R_int	0.052
(sin θ/λ)_max (Å⁻¹)	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.064, 0.170, 1.01
No. of reflections	3008
No. of parameters	167
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.28, −0.36

Computer programs: CrystalClear (Rigaku, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL/PC (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N4—H4A···O2ⁱ	0.86	2.32	3.093 (3)	149.4
N4—H4B···N2ⁱⁱ	0.86	2.57	3.420 (3)	172.1

Symmetry codes: (i) −x, −y+1, −z+1; (ii) x−1, y, z.

Acknowledgements

This work was supported by the National S&T Major Special Project on Major New Drug Innovation (grant No. 2009ZX09301-003).

References

Fancelli, D., et al. (2005). J. Med. Chem. 48, 3080–3084 Web of Science CrossRef PubMed CAS Google Scholar
Gadekar, S. M., Johnson, B. D. & Cohen, E. (1968). J. Med. Chem. 11, 616–618. CrossRef CAS PubMed Web of Science Google Scholar
Rigaku (2005). CrystalClear. Rigaku Corporation, Tokyo, Japan. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 66| Part 5| May 2010| Page o1108

https://doi.org/10.1107/S1600536810013218

Open

access

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text

Search IUCr Journals		doi		Advanced search
Author		volume	page

organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

tert-Butyl 3-amino-2-methyl-6,7-di­hydro-2H-pyrazolo[4,3-c]pyridine-5(4H)-carboxyl­ate

Related literature

Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

tert-Butyl 3-amino-2-methyl-6,7-dihydro-2H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate