supplementary materials


HTML versionpdf versioncif file3d viewstructure factorssupplementary materialsCIF check reportsimilar papers Open access

rz2434 scheme

Acta Cryst. (2010). E66, o1108    [ doi:10.1107/S1600536810013218 ]

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

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

Abstract top

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.

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.

Refinement top

All H atoms were placed at calculated positions and refined as riding, with C—H = 0.96-0.97 Å, N—H = 0.86 Å, and with Uiso(H) = 1.2Ueq(C, N) or 1.5Ueq(C) for methyl H atoms.

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
[Figure 1] Fig. 1. The molecular structure of the title compound, showing the atomic numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
[Figure 2] 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
C12H20N4O2Z = 2
Mr = 252.32F(000) = 272
Triclinic, P1Dx = 1.270 Mg m−3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 6.3151 (13) ÅCell parameters from 5123 reflections
b = 9.3615 (19) Åθ = 3.2–27.5°
c = 11.215 (2) ŵ = 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 tube1737 reflections with I > 2σ(I)
graphiteRint = 0.052
Detector resolution: 13.6612 pixels mm-1θmax = 27.5°, θmin = 3.2°
ω scansh = −8→8
Absorption correction: multi-scan
(CrystalClear; Rigaku, 2005)		k = −12→12
Tmin = 0.972, Tmax = 0.985l = −14→14
6859 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.064Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.170H-atom parameters constrained
S = 1.01 w = 1/[σ2(Fo2) + (0.081P)2]
where P = (Fo2 + 2Fc2)/3
3008 reflections(Δ/σ)max < 0.001
167 parametersΔρmax = 0.28 e Å−3
0 restraintsΔρmin = −0.36 e Å−3
Crystal data top
C12H20N4O2γ = 87.733 (4)°
Mr = 252.32V = 659.8 (2) Å3
Triclinic, P1Z = 2
a = 6.3151 (13) ÅMo Kα radiation
b = 9.3615 (19) ŵ = 0.09 mm−1
c = 11.215 (2) ÅT = 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)
Tmin = 0.972, Tmax = 0.985Rint = 0.052
6859 measured reflectionsθmax = 27.5°
Refinement top
R[F2 > 2σ(F2)] = 0.064H-atom parameters constrained
wR(F2) = 0.170Δρmax = 0.28 e Å−3
S = 1.01Δρmin = −0.36 e Å−3
3008 reflectionsAbsolute structure: ?
167 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
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
xyzUiso*/Ueq
C10.3109 (4)0.0363 (3)0.6957 (2)0.0386 (6)
H1A0.2825−0.04080.64620.046*
H1B0.3436−0.00610.77440.046*
C20.5027 (4)0.1173 (3)0.6406 (2)0.0398 (6)
H2A0.56190.17130.70070.048*
H2B0.61130.04980.61250.048*
C30.4344 (4)0.2180 (2)0.5375 (2)0.0331 (6)
C40.2211 (4)0.2453 (3)0.5144 (2)0.0329 (5)
C50.0400 (4)0.1836 (3)0.59148 (19)0.0385 (6)
H5A−0.07100.25670.60300.046*
H5B−0.01910.10570.55310.046*
C60.2214 (4)0.3437 (3)0.4173 (2)0.0346 (6)
C70.5130 (4)0.4687 (3)0.2914 (2)0.0479 (7)
H7A0.39840.51940.25220.072*
H7B0.59740.41620.23440.072*
H7C0.59970.53580.32510.072*
C80.0740 (4)0.2085 (3)0.8027 (2)0.0327 (5)
C90.1596 (4)0.2266 (3)1.0122 (2)0.0371 (6)
C100.2487 (5)0.3756 (3)0.9930 (3)0.0561 (8)
H10A0.39340.36840.96220.084*
H10B0.24310.41971.06790.084*
H10C0.16600.43290.93690.084*
C11−0.0678 (4)0.2267 (3)1.0624 (2)0.0486 (7)
H11A−0.15320.29191.01360.073*
H11B−0.07390.25631.14270.073*
H11C−0.12060.13191.06270.073*
C120.2991 (5)0.1310 (3)1.0927 (2)0.0564 (8)
H12A0.24570.03601.10080.085*
H12B0.29840.16871.17010.085*
H12C0.44160.12791.05800.085*
N10.1203 (3)0.1310 (2)0.70667 (17)0.0353 (5)
N20.5648 (3)0.2928 (2)0.46032 (17)0.0388 (5)
N30.4281 (3)0.3700 (2)0.38587 (17)0.0386 (5)
N40.0539 (3)0.4037 (2)0.35407 (19)0.0507 (6)
H4A0.07810.46060.29150.061*
H4B−0.07440.38400.37730.061*
O10.1814 (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
U11U22U33U12U13U23
C10.0362 (14)0.0381 (14)0.0400 (14)0.0063 (11)0.0030 (11)−0.0011 (11)
C20.0327 (14)0.0447 (15)0.0402 (14)0.0078 (11)0.0001 (11)0.0032 (12)
C30.0273 (12)0.0387 (14)0.0327 (12)0.0038 (10)−0.0009 (10)−0.0015 (11)
C40.0268 (12)0.0436 (14)0.0285 (12)0.0024 (10)−0.0019 (9)−0.0044 (10)
C50.0308 (13)0.0529 (16)0.0319 (13)−0.0022 (11)−0.0021 (10)−0.0040 (12)
C60.0296 (13)0.0445 (14)0.0299 (12)0.0033 (11)−0.0042 (10)−0.0053 (11)
C70.0437 (16)0.0557 (17)0.0420 (15)−0.0021 (13)0.0000 (12)0.0110 (13)
C80.0271 (12)0.0374 (13)0.0323 (12)−0.0002 (11)0.0005 (10)0.0037 (11)
C90.0413 (15)0.0385 (14)0.0312 (13)−0.0011 (11)−0.0013 (10)−0.0018 (11)
C100.0587 (19)0.0517 (18)0.0591 (18)−0.0151 (14)−0.0054 (14)−0.0026 (14)
C110.0493 (17)0.0514 (17)0.0440 (15)−0.0054 (13)0.0103 (13)−0.0028 (13)
C120.065 (2)0.0602 (19)0.0440 (16)0.0080 (15)−0.0120 (14)0.0000 (14)
N10.0302 (11)0.0431 (12)0.0317 (10)0.0020 (9)0.0024 (8)−0.0015 (9)
N20.0274 (11)0.0496 (13)0.0376 (11)0.0047 (9)−0.0007 (9)0.0052 (10)
N30.0292 (11)0.0487 (13)0.0360 (11)0.0037 (9)−0.0020 (9)0.0067 (10)
N40.0365 (13)0.0750 (17)0.0386 (12)0.0059 (11)−0.0059 (10)0.0092 (11)
O10.0475 (11)0.0406 (10)0.0307 (9)0.0096 (8)−0.0045 (7)−0.0031 (7)
O20.0519 (12)0.0496 (11)0.0403 (10)0.0201 (9)−0.0040 (8)0.0006 (8)
Geometric parameters (Å, °) top
C1—N11.471 (3)C8—O21.227 (3)
C1—C21.532 (3)C8—O11.349 (3)
C1—H1A0.9700C8—N11.354 (3)
C1—H1B0.9700C9—O11.474 (3)
C2—C31.509 (3)C9—C111.513 (3)
C2—H2A0.9700C9—C121.516 (3)
C2—H2B0.9700C9—C101.521 (3)
C3—N21.340 (3)C10—H10A0.9600
C3—C41.396 (3)C10—H10B0.9600
C4—C61.375 (3)C10—H10C0.9600
C4—C51.502 (3)C11—H11A0.9600
C5—N11.460 (3)C11—H11B0.9600
C5—H5A0.9700C11—H11C0.9600
C5—H5B0.9700C12—H12A0.9600
C6—N31.360 (3)C12—H12B0.9600
C6—N41.384 (3)C12—H12C0.9600
C7—N31.448 (3)N2—N31.382 (3)
C7—H7A0.9600N4—H4A0.8600
C7—H7B0.9600N4—H4B0.8600
C7—H7C0.9600
N1—C1—C2111.82 (19)O1—C9—C11111.03 (19)
N1—C1—H1A109.3O1—C9—C12102.7 (2)
C2—C1—H1A109.3C11—C9—C12110.1 (2)
N1—C1—H1B109.3O1—C9—C10108.8 (2)
C2—C1—H1B109.3C11—C9—C10113.5 (2)
H1A—C1—H1B107.9C12—C9—C10110.2 (2)
C3—C2—C1109.5 (2)C9—C10—H10A109.5
C3—C2—H2A109.8C9—C10—H10B109.5
C1—C2—H2A109.8H10A—C10—H10B109.5
C3—C2—H2B109.8C9—C10—H10C109.5
C1—C2—H2B109.8H10A—C10—H10C109.5
H2A—C2—H2B108.2H10B—C10—H10C109.5
N2—C3—C4112.4 (2)C9—C11—H11A109.5
N2—C3—C2125.5 (2)C9—C11—H11B109.5
C4—C3—C2122.1 (2)H11A—C11—H11B109.5
C6—C4—C3105.4 (2)C9—C11—H11C109.5
C6—C4—C5130.6 (2)H11A—C11—H11C109.5
C3—C4—C5123.8 (2)H11B—C11—H11C109.5
N1—C5—C4108.28 (18)C9—C12—H12A109.5
N1—C5—H5A110.0C9—C12—H12B109.5
C4—C5—H5A110.0H12A—C12—H12B109.5
N1—C5—H5B110.0C9—C12—H12C109.5
C4—C5—H5B110.0H12A—C12—H12C109.5
H5A—C5—H5B108.4H12B—C12—H12C109.5
N3—C6—C4106.7 (2)C8—N1—C5118.53 (19)
N3—C6—N4123.2 (2)C8—N1—C1122.99 (19)
C4—C6—N4129.9 (2)C5—N1—C1113.39 (19)
N3—C7—H7A109.5C3—N2—N3103.51 (18)
N3—C7—H7B109.5C6—N3—N2111.98 (19)
H7A—C7—H7B109.5C6—N3—C7128.4 (2)
N3—C7—H7C109.5N2—N3—C7119.56 (19)
H7A—C7—H7C109.5C6—N4—H4A120.0
H7B—C7—H7C109.5C6—N4—H4B120.0
O2—C8—O1124.3 (2)H4A—N4—H4B120.0
O2—C8—N1124.0 (2)C8—O1—C9121.18 (18)
O1—C8—N1111.59 (19)
N1—C1—C2—C3−42.3 (3)C4—C5—N1—C8104.8 (2)
C1—C2—C3—N2−171.7 (2)C4—C5—N1—C1−50.8 (3)
C1—C2—C3—C49.9 (3)C2—C1—N1—C8−86.9 (3)
N2—C3—C4—C6−0.3 (3)C2—C1—N1—C567.4 (2)
C2—C3—C4—C6178.3 (2)C4—C3—N2—N30.0 (3)
N2—C3—C4—C5−175.9 (2)C2—C3—N2—N3−178.6 (2)
C2—C3—C4—C52.8 (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—N116.7 (3)C4—C6—N3—C7−178.1 (2)
C3—C4—C6—N30.6 (3)N4—C6—N3—C75.1 (4)
C5—C4—C6—N3175.7 (2)C3—N2—N3—C60.4 (2)
C3—C4—C6—N4177.1 (2)C3—N2—N3—C7178.1 (2)
C5—C4—C6—N4−7.8 (4)O2—C8—O1—C9−2.9 (3)
O2—C8—N1—C59.7 (3)N1—C8—O1—C9178.62 (19)
O1—C8—N1—C5−171.83 (18)C11—C9—O1—C860.3 (3)
O2—C8—N1—C1162.8 (2)C12—C9—O1—C8177.9 (2)
O1—C8—N1—C1−18.7 (3)C10—C9—O1—C8−65.3 (3)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N4—H4A···O2i0.862.323.093 (3)149
N4—H4B···N2ii0.862.573.420 (3)172
Symmetry codes: (i) −x, −y+1, −z+1; (ii) x−1, y, z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N4—H4A···O2i0.862.323.093 (3)149
N4—H4B···N2ii0.862.573.420 (3)172
Symmetry codes: (i) −x, −y+1, −z+1; (ii) x−1, y, z.
Acknowledgements top

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

references
References top

Fancelli, D., et al. (2005). J. Med. Chem. 48, 3080–3084

Gadekar, S. M., Johnson, B. D. & Cohen, E. (1968). J. Med. Chem. 11, 616–618.

Rigaku (2005). CrystalClear. Rigaku Corporation, Tokyo, Japan.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.