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Acta Crystallogr Sect E Struct Rep Online. 2010 May 1; 66(Pt 5): o1108.
Published online 2010 April 17. doi:  10.1107/S1600536810013218
PMCID: PMC2979268

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

Abstract

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 [triangle]); Gadekar et al. (1968 [triangle]).

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Object name is e-66-o1108-scheme1.jpg

Experimental

Crystal data

  • C12H20N4O2
  • M r = 252.32
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o1108-efi1.jpg
  • 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 [triangle]) 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[F 2 > 2σ(F 2)] = 0.064
  • wR(F 2) = 0.170
  • S = 1.01
  • 3008 reflections
  • 167 parameters
  • H-atom parameters constrained
  • Δρmax = 0.28 e Å−3
  • Δρmin = −0.36 e Å−3

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

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

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

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810013218/rz2434Isup2.hkl

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

Acknowledgments

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

supplementary crystallographic information

Comment

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.

Experimental

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

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.

Figures

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.

Crystal data

C12H20N4O2Z = 2
Mr = 252.32F(000) = 272
Triclinic, P1Dx = 1.270 Mg m3
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 mm1
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

Rigaku, SCXmini diffractometer3008 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

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 = 1.01w = 1/[σ2(Fo2) + (0.081P)2] where P = (Fo2 + 2Fc2)/3
3008 reflections(Δ/σ)max < 0.001
167 parametersΔρmax = 0.28 e Å3
0 restraintsΔρmin = −0.36 e Å3

Special details

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)

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)

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, °)

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, °)

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.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: RZ2434).

References

  • Fancelli, D., et al. (2005). J. Med. Chem.48, 3080–3084 [PubMed]
  • Gadekar, S. M., Johnson, B. D. & Cohen, E. (1968). J. Med. Chem.11, 616–618. [PubMed]
  • Rigaku (2005). CrystalClear Rigaku Corporation, Tokyo, Japan.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

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