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organic compounds
2-Methyl-3-(1H-pyrazol-3-yl)imidazo[1,2-a]pyrimidine
aSchool of Pharmacy, East China University of Science and Technology, Shanghai 200237, People's Republic of China, and bDepartment of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China
*Correspondence e-mail: whduan@mail.shcnc.ac.cn
In the title compound, C10H9N5, the fused 2-methylimidazo[1,2-a]pyrimidine ring system is approximately planar [dihedral angle of 1.14 (9)° between the two fused rings] and the 1H-pyrazole ring is rotated by 28.16 (11)° out of that plane. In the crystal, the molecules are linked into linear chains along the [100] direction by classical intermolecular N—H⋯N hydrogen bonds.
Related literature
For the medical properties of imidazo[1,2-a]pyrimidine derivatives, see: An et al. (2009); Kim et al. (2011
); Linton et al. (2011
). For related structures, see: Yang et al. (2008
); Anaflous et al. (2004
).
Experimental
Crystal data
|
Refinement
|
|
Data collection: SMART (Bruker, 2000); cell SMART; data reduction: SAINT (Bruker, 2000
); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008
); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008
); molecular graphics: SHELXTL (Sheldrick, 2008
); software used to prepare material for publication: SHELXTL.
Supporting information
https://doi.org/10.1107/S1600536812024166/rk2359sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812024166/rk2359Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S1600536812024166/rk2359Isup3.cml
A mixture of 1-(2-methylimidazo[1,2-a]pyrimidin-3-yl)ethanone (500 mg, 2.86 mmol) and 1,1-dimethoxy-N,N-dimethylmethanamine (3.8 ml, 28.6 mmol) was heated at 373 K for 6 h. After cooling to room temperature, EtOH (10 ml) and hydrazine hydrate (0.28 ml, 5.72 mmol) were added and the reaction mixture was refluxed for 3 h. The mixture was diluted with water and extracted with CH2Cl2. The organic layer was dried over MgSO4 and evaporated. The crude product was chromatographed on silica gel eluting with DCM–MeOH (10/1) to give the title compound as a pale-yellow solid (300 mg, yield: 52%).
H atoms attached to NH group and methyl C atoms were located in a difference Fourier map and refined isotropically. The other H atoms attached to C atoms were positioned with idealized geometry (C—H = 0.95Å) using a riding model with Uiso(H) = 1.2Ueq(C).
Imidazo[1,2-a]pyrimidine derivatives have been used for treatment of cancers (An et al., 2009; Kim et al., 2011; Linton et al., 2011), and some analogues were reported (Anaflous et al., 2004; Yang et al., 2008). The title compound was synthesized by the reaction of 1-(2-methylimidazo[1,2-a]pyrimidin-3-yl)ethanone with 1,1-dimethoxy-N,N-dimethylmethanamine, and its
was confirmed by single crystal X-ray analysis (Fig. 1). In this compound, the fused 2-methylimidazo[1,2-a]pyrimidine ring system are approximately coplanar with a tiny dihedral angle being 1.14 (9)°, but the 1H-pyrazole ring is rotated 28.16 (11)° out of the the fused 2-methylimidazo[1,2-a]pyrimidine ring system plane. Further analysis showed that each molecule is associated with two neighbors to generate an infinite one-dimensional chain extending along the [1 0 0] direction with the formation classical intermolecular N12—H30A···N6i hydrogen bond (Fig. 2). Symmetry code: (i) x - 1, y, z. The relevant parameters are listed in Table 1.For the medical properties of imidazo[1,2-a]pyrimidine derivatives, see: An et al. (2009); Kim et al. (2011); Linton et al. (2011). For related structures, see: Yang et al. (2008); Anaflous et al. (2004).
Data collection: SMART (Bruker, 2000); cell
SMART (Bruker, 2000); data reduction: SAINT (Bruker, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).C10H9N5 | F(000) = 416 |
Mr = 199.22 | Dx = 1.365 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2yn | Cell parameters from 1511 reflections |
a = 8.962 (2) Å | θ = 2.6–24.0° |
b = 8.851 (2) Å | µ = 0.09 mm−1 |
c = 12.481 (3) Å | T = 173 K |
β = 101.751 (3)° | Bar, pale yellow |
V = 969.3 (4) Å3 | 0.50 × 0.10 × 0.08 mm |
Z = 4 |
Bruker SMART APEX CCD diffractometer | 1907 independent reflections |
Radiation source: fine-focus sealed tube | 1552 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.024 |
φ and ω scans | θmax = 26.0°, θmin = 2.6° |
Absorption correction: multi-scan (SADABS; Bruker, 2000) | h = −10→11 |
Tmin = 0.956, Tmax = 0.993 | k = −10→10 |
5121 measured reflections | l = −15→8 |
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)] = 0.051 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.128 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.09 | w = 1/[σ2(Fo2) + (0.0572P)2 + 0.2361P] where P = (Fo2 + 2Fc2)/3 |
1907 reflections | (Δ/σ)max < 0.001 |
152 parameters | Δρmax = 0.20 e Å−3 |
0 restraints | Δρmin = −0.14 e Å−3 |
C10H9N5 | V = 969.3 (4) Å3 |
Mr = 199.22 | Z = 4 |
Monoclinic, P21/n | Mo Kα radiation |
a = 8.962 (2) Å | µ = 0.09 mm−1 |
b = 8.851 (2) Å | T = 173 K |
c = 12.481 (3) Å | 0.50 × 0.10 × 0.08 mm |
β = 101.751 (3)° |
Bruker SMART APEX CCD diffractometer | 1907 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2000) | 1552 reflections with I > 2σ(I) |
Tmin = 0.956, Tmax = 0.993 | Rint = 0.024 |
5121 measured reflections |
R[F2 > 2σ(F2)] = 0.051 | 0 restraints |
wR(F2) = 0.128 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.09 | Δρmax = 0.20 e Å−3 |
1907 reflections | Δρmin = −0.14 e Å−3 |
152 parameters |
Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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. |
x | y | z | Uiso*/Ueq | ||
N4 | 0.44313 (15) | 0.15343 (16) | 0.08173 (12) | 0.0371 (4) | |
N1 | 0.65249 (16) | 0.11695 (18) | 0.21150 (13) | 0.0455 (4) | |
N6 | 0.68599 (17) | 0.2102 (2) | 0.03899 (14) | 0.0495 (4) | |
C3 | 0.39442 (19) | 0.0960 (2) | 0.17190 (15) | 0.0376 (4) | |
N12 | −0.00496 (19) | 0.0927 (2) | 0.13228 (16) | 0.0531 (5) | |
C5 | 0.60176 (19) | 0.1626 (2) | 0.11018 (15) | 0.0401 (4) | |
C9 | 0.3688 (2) | 0.1977 (2) | −0.01970 (16) | 0.0475 (5) | |
H9A | 0.2609 | 0.1930 | −0.0399 | 0.057* | |
C10 | 0.23463 (19) | 0.0676 (2) | 0.17285 (15) | 0.0399 (4) | |
N11 | 0.12533 (17) | 0.14869 (19) | 0.10998 (14) | 0.0492 (5) | |
C2 | 0.5255 (2) | 0.0765 (2) | 0.24983 (15) | 0.0431 (5) | |
C13 | 0.0186 (2) | −0.0174 (2) | 0.2049 (2) | 0.0565 (6) | |
H13A | −0.0573 | −0.0719 | 0.2319 | 0.068* | |
C8 | 0.4521 (2) | 0.2482 (3) | −0.09045 (17) | 0.0560 (6) | |
H8A | 0.4038 | 0.2812 | −0.1615 | 0.067* | |
C14 | 0.1724 (2) | −0.0382 (2) | 0.23391 (19) | 0.0536 (5) | |
H14A | 0.2255 | −0.1094 | 0.2847 | 0.064* | |
C7 | 0.6118 (2) | 0.2516 (3) | −0.05784 (18) | 0.0560 (6) | |
H7A | 0.6692 | 0.2859 | −0.1092 | 0.067* | |
C15 | 0.5385 (3) | 0.0238 (4) | 0.3649 (2) | 0.0648 (7) | |
H30A | −0.095 (3) | 0.129 (3) | 0.1009 (18) | 0.061 (7)* | |
H15C | 0.478 (4) | −0.057 (4) | 0.372 (3) | 0.130 (13)* | |
H15B | 0.639 (4) | −0.005 (4) | 0.396 (3) | 0.119 (12)* | |
H15A | 0.512 (5) | 0.106 (6) | 0.410 (4) | 0.184 (19)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N4 | 0.0254 (7) | 0.0391 (8) | 0.0440 (9) | 0.0020 (6) | 0.0003 (6) | −0.0010 (6) |
N1 | 0.0289 (8) | 0.0517 (10) | 0.0521 (10) | −0.0001 (7) | −0.0008 (7) | 0.0043 (7) |
N6 | 0.0318 (9) | 0.0591 (10) | 0.0575 (11) | −0.0004 (7) | 0.0089 (7) | 0.0040 (8) |
C3 | 0.0303 (9) | 0.0368 (9) | 0.0446 (10) | 0.0011 (7) | 0.0051 (7) | −0.0007 (8) |
N12 | 0.0259 (9) | 0.0593 (11) | 0.0735 (12) | 0.0001 (7) | 0.0086 (8) | 0.0012 (9) |
C5 | 0.0259 (9) | 0.0429 (10) | 0.0492 (11) | 0.0010 (7) | 0.0026 (7) | −0.0013 (8) |
C9 | 0.0325 (10) | 0.0550 (12) | 0.0504 (11) | 0.0036 (8) | −0.0024 (8) | 0.0025 (9) |
C10 | 0.0305 (9) | 0.0376 (10) | 0.0506 (11) | 0.0012 (7) | 0.0060 (8) | −0.0044 (8) |
N11 | 0.0265 (8) | 0.0531 (10) | 0.0666 (11) | 0.0001 (7) | 0.0063 (7) | 0.0046 (8) |
C2 | 0.0344 (10) | 0.0436 (11) | 0.0485 (11) | −0.0003 (8) | 0.0019 (8) | 0.0015 (8) |
C13 | 0.0412 (11) | 0.0518 (12) | 0.0803 (16) | −0.0067 (9) | 0.0212 (10) | 0.0038 (11) |
C8 | 0.0467 (12) | 0.0715 (14) | 0.0474 (12) | 0.0043 (10) | 0.0040 (9) | 0.0095 (10) |
C14 | 0.0393 (11) | 0.0500 (12) | 0.0720 (14) | 0.0008 (9) | 0.0124 (10) | 0.0112 (10) |
C7 | 0.0455 (12) | 0.0683 (14) | 0.0565 (13) | −0.0008 (10) | 0.0156 (10) | 0.0093 (11) |
C15 | 0.0530 (15) | 0.0809 (18) | 0.0544 (14) | −0.0088 (13) | −0.0037 (11) | 0.0185 (13) |
N4—C9 | 1.362 (2) | C9—H9A | 0.9500 |
N4—C3 | 1.384 (2) | C10—N11 | 1.333 (2) |
N4—C5 | 1.396 (2) | C10—C14 | 1.394 (3) |
N1—C5 | 1.317 (2) | C2—C15 | 1.492 (3) |
N1—C2 | 1.369 (2) | C13—C14 | 1.364 (3) |
N6—C7 | 1.307 (3) | C13—H13A | 0.9500 |
N6—C5 | 1.345 (2) | C8—C7 | 1.406 (3) |
C3—C2 | 1.375 (2) | C8—H8A | 0.9500 |
C3—C10 | 1.456 (2) | C14—H14A | 0.9500 |
N12—C13 | 1.318 (3) | C7—H7A | 0.9500 |
N12—N11 | 1.349 (2) | C15—H15C | 0.92 (4) |
N12—H30A | 0.89 (2) | C15—H15B | 0.94 (4) |
C9—C8 | 1.343 (3) | C15—H15A | 0.98 (5) |
C9—N4—C3 | 133.30 (15) | N1—C2—C3 | 111.79 (17) |
C9—N4—C5 | 119.96 (16) | N1—C2—C15 | 120.70 (18) |
C3—N4—C5 | 106.74 (14) | C3—C2—C15 | 127.5 (2) |
C5—N1—C2 | 105.47 (14) | N12—C13—C14 | 107.10 (18) |
C7—N6—C5 | 116.74 (17) | N12—C13—H13A | 126.4 |
C2—C3—N4 | 104.82 (16) | C14—C13—H13A | 126.4 |
C2—C3—C10 | 132.26 (18) | C9—C8—C7 | 119.0 (2) |
N4—C3—C10 | 122.92 (15) | C9—C8—H8A | 120.5 |
C13—N12—N11 | 112.94 (17) | C7—C8—H8A | 120.5 |
C13—N12—H30A | 125.4 (15) | C13—C14—C10 | 105.02 (19) |
N11—N12—H30A | 121.7 (15) | C13—C14—H14A | 127.5 |
N1—C5—N6 | 126.85 (16) | C10—C14—H14A | 127.5 |
N1—C5—N4 | 111.16 (16) | N6—C7—C8 | 123.9 (2) |
N6—C5—N4 | 121.98 (17) | N6—C7—H7A | 118.0 |
C8—C9—N4 | 118.35 (17) | C8—C7—H7A | 118.0 |
C8—C9—H9A | 120.8 | C2—C15—H15C | 114 (2) |
N4—C9—H9A | 120.8 | C2—C15—H15B | 111 (2) |
N11—C10—C14 | 110.84 (17) | H15C—C15—H15B | 106 (3) |
N11—C10—C3 | 120.54 (17) | C2—C15—H15A | 110 (3) |
C14—C10—C3 | 128.62 (17) | H15C—C15—H15A | 108 (3) |
C10—N11—N12 | 104.10 (16) | H15B—C15—H15A | 107 (3) |
C9—N4—C3—C2 | −178.99 (18) | N4—C3—C10—C14 | 152.1 (2) |
C5—N4—C3—C2 | 1.06 (19) | C14—C10—N11—N12 | 0.0 (2) |
C9—N4—C3—C10 | 1.0 (3) | C3—C10—N11—N12 | −179.70 (16) |
C5—N4—C3—C10 | −178.91 (16) | C13—N12—N11—C10 | 0.0 (2) |
C2—N1—C5—N6 | −178.49 (18) | C5—N1—C2—C3 | 0.3 (2) |
C2—N1—C5—N4 | 0.4 (2) | C5—N1—C2—C15 | −177.7 (2) |
C7—N6—C5—N1 | −179.55 (19) | N4—C3—C2—N1 | −0.9 (2) |
C7—N6—C5—N4 | 1.7 (3) | C10—C3—C2—N1 | 179.06 (18) |
C9—N4—C5—N1 | 179.12 (16) | N4—C3—C2—C15 | 177.0 (2) |
C3—N4—C5—N1 | −0.9 (2) | C10—C3—C2—C15 | −3.0 (4) |
C9—N4—C5—N6 | −2.0 (3) | N11—N12—C13—C14 | −0.1 (3) |
C3—N4—C5—N6 | 177.99 (17) | N4—C9—C8—C7 | 0.8 (3) |
C3—N4—C9—C8 | −179.3 (2) | N12—C13—C14—C10 | 0.0 (3) |
C5—N4—C9—C8 | 0.6 (3) | N11—C10—C14—C13 | 0.0 (2) |
C2—C3—C10—N11 | 151.8 (2) | C3—C10—C14—C13 | 179.63 (19) |
N4—C3—C10—N11 | −28.2 (3) | C5—N6—C7—C8 | −0.2 (3) |
C2—C3—C10—C14 | −27.8 (3) | C9—C8—C7—N6 | −1.1 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
N12—H30A···N6i | 0.89 (2) | 2.08 (2) | 2.966 (2) | 175 (2) |
Symmetry code: (i) x−1, y, z. |
Experimental details
Crystal data | |
Chemical formula | C10H9N5 |
Mr | 199.22 |
Crystal system, space group | Monoclinic, P21/n |
Temperature (K) | 173 |
a, b, c (Å) | 8.962 (2), 8.851 (2), 12.481 (3) |
β (°) | 101.751 (3) |
V (Å3) | 969.3 (4) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.50 × 0.10 × 0.08 |
Data collection | |
Diffractometer | Bruker SMART APEX CCD |
Absorption correction | Multi-scan (SADABS; Bruker, 2000) |
Tmin, Tmax | 0.956, 0.993 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 5121, 1907, 1552 |
Rint | 0.024 |
(sin θ/λ)max (Å−1) | 0.617 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.051, 0.128, 1.09 |
No. of reflections | 1907 |
No. of parameters | 152 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.20, −0.14 |
Computer programs: SMART (Bruker, 2000), SAINT (Bruker, 2000), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).
D—H···A | D—H | H···A | D···A | D—H···A |
N12—H30A···N6i | 0.89 (2) | 2.08 (2) | 2.966 (2) | 175 (2) |
Symmetry code: (i) x−1, y, z. |
Acknowledgements
The authors thank the National Natural Science Foundation (grant Nos. 81102461, 81021062 and 90813034) and the National Science and Technology Major Project `Key New Drug Creation and Manufacturing Program' (grant Nos. 2012ZX09301-001-007 and 2012ZX09103101-024) of the People's Republic of China, and the Shanghai Science and Technology Commission (grant No. 11431921100).
References
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Imidazo[1,2-a]pyrimidine derivatives have been used for treatment of cancers (An et al., 2009; Kim et al., 2011; Linton et al., 2011), and some analogues were reported (Anaflous et al., 2004; Yang et al., 2008). The title compound was synthesized by the reaction of 1-(2-methylimidazo[1,2-a]pyrimidin-3-yl)ethanone with 1,1-dimethoxy-N,N-dimethylmethanamine, and its crystal structure was confirmed by single crystal X-ray analysis (Fig. 1). In this compound, the fused 2-methylimidazo[1,2-a]pyrimidine ring system are approximately coplanar with a tiny dihedral angle being 1.14 (9)°, but the 1H-pyrazole ring is rotated 28.16 (11)° out of the the fused 2-methylimidazo[1,2-a]pyrimidine ring system plane. Further analysis showed that each molecule is associated with two neighbors to generate an infinite one-dimensional chain extending along the [1 0 0] direction with the formation classical intermolecular N12—H30A···N6i hydrogen bond (Fig. 2). Symmetry code: (i) x - 1, y, z. The relevant parameters are listed in Table 1.