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Acta Cryst. (2007). E63, o2843    [ doi:10.1107/S1600536807021484 ]

3-[(2-Chlorothiazol-5-yl)methyl]-5-(isobutylamino)-6-phenyl-3H-1,2,3-triazolo[4,5-d]pyrimidin-7(6H)-one

L.-X. Xiao and D.-Q. Shi

Abstract top

The title compound, C18H18ClN7OS, the mean plane of the triazolopyrimidine system makes dihedral angles of 77.54 (13) and 80.15 (13)°, respectively, with the attached phenyl and 2-chlorothiazole rings. The crystal packing is stabilized by intermolecular N-H...N hydrogen bonds and weak [pi]-[pi] stacking interactions [the interplanar distance is 3.724 (2) Å].

Comment top

8-aza analogues of similarly substituted purines ([1,2,3]triazolo[4,5-d]pyrimidines are one such example) have been synthesized in recent years, and many of them exhibit broad spectral biological activities, such as the interesting antifungal (Roblin et al., 1945), antiviral (Shealy et al., 1984), anticancer (Kidder et al., 1951) and antiallergic (Lunt, 1982) activities. Recently, we have developed a versatile method via tandem aza-Wittig, followed by the cyclization to synthesize the novel triazolo[4,5-d]-pyrimidine derivatives (Ding et al., 2004; Wang et al., 2004). In this paper, we report the structure of the title compound, (I) (Fig. 1). In the triazolopyrimidine ring, the C5—N2, C5—N6, C6—N4, C7—N5 and C8—N5 bonds, Tabel 1, are significantly shorter than a normal single C—N bond (1.47 Å; Sasada, 1984) and closer to the value for a C═N bond (1.28 Å; Wang et al., 1998). This indicates significant electron delocalization in the triazolo[4,5-d]pyrimidinyl system.

In the crystal structure, intermolecular N—H···N hydrogen-bonds contribute strongly to the stability of the molecular configuration (Fig.2 and Table 1). In addition, short intermolecular distances between the centroids of the C1–C2/N1/S1 ring (Cg1) and the C13–C18 ring (Cg4) of the adjacent molecule indicate the existence of weak π— π stacking interactions [Cg1···Cg4i =3.7237 (20) Å, dihedral angles of 5.94 (16)°, and a shortest interplanar distance of 3.388 Å.; symmetry code: (i) 1/2 + x, -1/2 + y, z.

Related literature top

For biological activities of 8-aza purines, see: Roblin et al. (1945); Shealy et al. (1984); Kidder et al. (1951); Lunt (1982). For the synthesis of triazolopyrimidine compounds, see: Ding et al. (2004); Wang et al. (2004).

For related literature, see: Sasada (1984); Wang et al. (1998).

Experimental top

To a suspension of ethyl 1-((2-chlorothiazol-5-yl)methyl)- 5-((isobutylamino)(phenyl)methyleneamino)-1H-1,2,3-triazole-4-carboxylate (0.92 g, 2 mmol) in 10 ml of anhydrous ethanol, several drops of EtONa in EtOH were added at room temperature. The mixture was stirred for 10 min (monitored by thin layer chromatography), then the solution concentrated under vacuum and the residue was recrystallized from dichloromethane to give the title compound (yield 76%). Colourless crystals of (I) suitable for X-ray structure analysis were grown from a mixture of dichloromethane and ethanol (v/v, 1:3).

Refinement top

All H atoms were placed in calculated positions, with C—H distances in the range 0.93–0.97 Å and N—H distances of 0.77–0.88 Å, and included in the final cycles of refinement using a riding-model approximation, with Uiso(H) = 1.2–1.5Ueq(carrier atom).

Computing details top

Data collection: SMART (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1997); software used to prepare material for publication: SHELXTL.

Figures top
[Figure 1] Fig. 1. The structure of (I), showing 50% probability displacement ellipsoids and the atom-numbering scheme.
[Figure 2] Fig. 2. Crystal packing diagram of (I). Hydrogen bonds are shown as dashed lines.
3-[(2-Chlorothiazol-5-yl)methyl]-5-(isobutylamino)-6-phenyl-3H- 1,2,3-triazolo[4,5-d]pyrimidin-7(6H)-one top
Crystal data top
C18H18ClN7OSF(000) = 1728
Mr = 415.90Dx = 1.380 Mg m−3
Monoclinic, C2/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2ycCell parameters from 1064 reflections
a = 20.0916 (18) Åθ = 2.8–16.5°
b = 7.2538 (7) ŵ = 0.32 mm−1
c = 28.046 (2) ÅT = 294 K
β = 101.527 (2)°Block, colorless
V = 4005.0 (6) Å30.20 × 0.10 × 0.04 mm
Z = 8
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer		4343 independent reflections
Radiation source: fine-focus sealed tube2226 reflections with I > 2σ(I)
graphiteRint = 0.096
φ and ω scansθmax = 27.0°, θmin = 1.5°
Absorption correction: multi-scan
(SADABS; Sheldrick, 2001)		h = −25→25
Tmin = 0.939, Tmax = 0.987k = −9→9
17095 measured reflectionsl = −33→35
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) = 0.143H-atom parameters constrained
S = 0.98 w = 1/[σ2(Fo2) + (0.0523P)2]
where P = (Fo2 + 2Fc2)/3
4343 reflections(Δ/σ)max = 0.001
255 parametersΔρmax = 0.28 e Å−3
0 restraintsΔρmin = −0.25 e Å−3
Crystal data top
C18H18ClN7OSV = 4005.0 (6) Å3
Mr = 415.90Z = 8
Monoclinic, C2/cMo Kα radiation
a = 20.0916 (18) ŵ = 0.32 mm−1
b = 7.2538 (7) ÅT = 294 K
c = 28.046 (2) Å0.20 × 0.10 × 0.04 mm
β = 101.527 (2)°
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer		4343 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 2001)		2226 reflections with I > 2σ(I)
Tmin = 0.939, Tmax = 0.987Rint = 0.096
17095 measured reflectionsθmax = 27.0°
Refinement top
R[F2 > 2σ(F2)] = 0.064H-atom parameters constrained
wR(F2) = 0.143Δρmax = 0.28 e Å−3
S = 0.98Δρmin = −0.25 e Å−3
4343 reflectionsAbsolute structure: ?
255 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
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
xyzUiso*/Ueq
C10.45437 (18)−0.1881 (5)0.07899 (12)0.0475 (9)
C20.49843 (16)−0.1194 (5)0.15347 (12)0.0456 (9)
H20.5333−0.10400.18050.055*
C30.43344 (15)−0.0848 (4)0.15564 (11)0.0357 (8)
C40.40458 (15)−0.0225 (5)0.19814 (11)0.0431 (9)
H4A0.4402−0.02240.22710.052*
H4B0.38800.10270.19250.052*
C50.28245 (15)−0.1132 (4)0.19072 (10)0.0331 (7)
C60.25197 (16)−0.2612 (4)0.20799 (11)0.0383 (8)
C70.17957 (17)−0.2757 (5)0.19767 (11)0.0387 (8)
C80.18729 (16)0.0218 (4)0.15449 (11)0.0351 (8)
C90.18402 (17)0.3310 (4)0.11911 (13)0.0482 (9)
H9A0.22180.35640.14570.058*
H9B0.15180.43120.11790.058*
C100.2099 (2)0.3308 (6)0.07249 (15)0.0692 (12)
H100.24720.24150.07570.083*
C110.1566 (3)0.2773 (7)0.02910 (14)0.1029 (17)
H11A0.14410.15080.03210.154*
H11B0.17430.29260.00000.154*
H11C0.11740.35440.02750.154*
C120.2385 (2)0.5219 (6)0.06524 (18)0.1065 (18)
H12A0.20280.61180.06230.160*
H12B0.25690.52220.03620.160*
H12C0.27370.55170.09270.160*
C130.07716 (15)−0.1286 (4)0.15216 (11)0.0341 (7)
C140.04907 (17)−0.1883 (5)0.10585 (11)0.0461 (9)
H140.0768−0.22740.08500.055*
C15−0.02078 (19)−0.1895 (5)0.09071 (13)0.0563 (10)
H15−0.0401−0.22820.05940.068*
C16−0.06186 (18)−0.1337 (5)0.12179 (15)0.0555 (10)
H16−0.1088−0.13480.11140.067*
C17−0.03405 (18)−0.0767 (5)0.16788 (14)0.0544 (10)
H17−0.0621−0.04010.18880.065*
C180.03624 (17)−0.0733 (4)0.18352 (12)0.0446 (9)
H180.0554−0.03410.21480.054*
Cl10.44869 (6)−0.26117 (17)0.02014 (3)0.0838 (4)
N10.51130 (14)−0.1786 (4)0.10948 (10)0.0489 (8)
N20.34916 (12)−0.1415 (4)0.20609 (9)0.0375 (7)
N30.36005 (14)−0.3031 (4)0.23214 (9)0.0474 (7)
N40.30135 (14)−0.3749 (4)0.23363 (9)0.0488 (8)
N50.15024 (12)−0.1259 (3)0.16775 (8)0.0361 (6)
N60.25402 (12)0.0313 (4)0.16422 (9)0.0368 (7)
N70.15143 (13)0.1615 (4)0.13001 (9)0.0426 (7)
H70.10820.15010.12060.051*
O10.14303 (12)−0.3936 (3)0.20981 (8)0.0531 (7)
S10.38275 (4)−0.12598 (13)0.09935 (3)0.0491 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.052 (2)0.052 (2)0.0397 (19)0.0035 (19)0.0133 (17)−0.0012 (17)
C20.035 (2)0.055 (2)0.045 (2)−0.0009 (18)0.0037 (15)−0.0014 (18)
C30.0272 (18)0.042 (2)0.0372 (18)0.0041 (15)0.0038 (14)0.0002 (15)
C40.0303 (19)0.056 (2)0.044 (2)−0.0006 (17)0.0084 (15)−0.0054 (17)
C50.0321 (18)0.040 (2)0.0281 (16)0.0018 (16)0.0090 (13)−0.0037 (15)
C60.037 (2)0.043 (2)0.0369 (18)0.0012 (17)0.0103 (15)0.0050 (16)
C70.042 (2)0.044 (2)0.0312 (17)−0.0009 (18)0.0085 (15)0.0017 (16)
C80.0321 (19)0.039 (2)0.0348 (18)0.0020 (16)0.0086 (14)0.0011 (15)
C90.041 (2)0.033 (2)0.068 (2)0.0025 (16)0.0060 (18)0.0090 (18)
C100.062 (3)0.068 (3)0.080 (3)−0.002 (2)0.020 (2)0.023 (2)
C110.114 (4)0.131 (5)0.061 (3)−0.028 (3)0.010 (3)0.007 (3)
C120.106 (4)0.087 (4)0.138 (5)−0.027 (3)0.052 (3)0.033 (3)
C130.0316 (18)0.0351 (19)0.0353 (18)−0.0028 (15)0.0061 (14)0.0012 (15)
C140.043 (2)0.055 (2)0.0396 (19)−0.0017 (18)0.0068 (16)−0.0028 (17)
C150.050 (2)0.064 (3)0.048 (2)−0.009 (2)−0.0092 (19)0.005 (2)
C160.033 (2)0.053 (2)0.076 (3)−0.0008 (19)0.001 (2)0.011 (2)
C170.040 (2)0.053 (2)0.074 (3)−0.0021 (18)0.022 (2)−0.003 (2)
C180.042 (2)0.051 (2)0.0417 (19)−0.0083 (17)0.0088 (16)−0.0063 (16)
Cl10.0986 (9)0.1105 (10)0.0437 (6)0.0133 (7)0.0175 (6)−0.0084 (6)
N10.0382 (17)0.060 (2)0.0487 (18)0.0021 (15)0.0101 (14)0.0000 (16)
N20.0318 (15)0.0440 (17)0.0366 (15)0.0012 (13)0.0068 (12)0.0025 (13)
N30.0419 (18)0.0529 (19)0.0474 (17)0.0120 (15)0.0090 (14)0.0155 (15)
N40.0411 (18)0.0506 (19)0.0550 (18)0.0101 (15)0.0105 (14)0.0185 (15)
N50.0287 (14)0.0424 (16)0.0371 (15)−0.0021 (13)0.0064 (11)0.0050 (13)
N60.0289 (16)0.0404 (16)0.0414 (15)0.0008 (13)0.0075 (12)0.0079 (13)
N70.0259 (14)0.0418 (17)0.0584 (17)−0.0007 (13)0.0042 (13)0.0138 (14)
O10.0468 (15)0.0507 (16)0.0617 (16)−0.0091 (13)0.0108 (12)0.0176 (13)
S10.0348 (5)0.0655 (7)0.0443 (5)0.0008 (5)0.0014 (4)−0.0024 (5)
Geometric parameters (Å, °) top
C1—N11.286 (4)C10—C111.503 (5)
C1—S11.711 (4)C10—C121.529 (5)
C1—Cl11.715 (3)C10—H100.9800
C2—C31.343 (4)C11—H11A0.9600
C2—N11.379 (4)C11—H11B0.9600
C2—H20.9300C11—H11C0.9600
C3—C41.496 (4)C12—H12A0.9600
C3—S11.725 (3)C12—H12B0.9600
C4—N21.460 (4)C12—H12C0.9600
C4—H4A0.9700C13—C181.378 (4)
C4—H4B0.9700C13—C141.378 (4)
C5—N21.339 (4)C13—N51.446 (4)
C5—N61.344 (4)C14—C151.383 (4)
C5—C61.372 (4)C14—H140.9300
C6—N41.377 (4)C15—C161.375 (5)
C6—C71.429 (4)C15—H150.9300
C7—O11.219 (3)C16—C171.366 (5)
C7—N51.426 (4)C16—H160.9300
C8—N61.316 (4)C17—C181.393 (4)
C8—N71.349 (4)C17—H170.9300
C8—N51.397 (4)C18—H180.9300
C9—N71.454 (4)N2—N31.376 (3)
C9—C101.501 (5)N3—N41.298 (3)
C9—H9A0.9700N7—H70.8600
C9—H9B0.9700
N1—C1—S1117.4 (3)C10—C11—H11C109.5
N1—C1—Cl1122.4 (3)H11A—C11—H11C109.5
S1—C1—Cl1120.3 (2)H11B—C11—H11C109.5
C3—C2—N1117.2 (3)C10—C12—H12A109.5
C3—C2—H2121.4C10—C12—H12B109.5
N1—C2—H2121.4H12A—C12—H12B109.5
C2—C3—C4128.9 (3)C10—C12—H12C109.5
C2—C3—S1109.1 (2)H12A—C12—H12C109.5
C4—C3—S1122.0 (2)H12B—C12—H12C109.5
N2—C4—C3111.8 (3)C18—C13—C14120.6 (3)
N2—C4—H4A109.2C18—C13—N5120.2 (3)
C3—C4—H4A109.2C14—C13—N5119.3 (3)
N2—C4—H4B109.2C13—C14—C15119.4 (3)
C3—C4—H4B109.2C13—C14—H14120.3
H4A—C4—H4B107.9C15—C14—H14120.3
N2—C5—N6125.8 (3)C16—C15—C14120.3 (3)
N2—C5—C6104.8 (3)C16—C15—H15119.9
N6—C5—C6129.4 (3)C14—C15—H15119.9
C5—C6—N4109.1 (3)C17—C16—C15120.3 (3)
C5—C6—C7119.6 (3)C17—C16—H16119.8
N4—C6—C7131.3 (3)C15—C16—H16119.8
O1—C7—N5119.8 (3)C16—C17—C18120.1 (3)
O1—C7—C6129.8 (3)C16—C17—H17120.0
N5—C7—C6110.3 (3)C18—C17—H17120.0
N6—C8—N7119.0 (3)C13—C18—C17119.4 (3)
N6—C8—N5124.1 (3)C13—C18—H18120.3
N7—C8—N5116.9 (3)C17—C18—H18120.3
N7—C9—C10115.6 (3)C1—N1—C2108.1 (3)
N7—C9—H9A108.4C5—N2—N3110.1 (3)
C10—C9—H9A108.4C5—N2—C4127.2 (3)
N7—C9—H9B108.4N3—N2—C4122.6 (3)
C10—C9—H9B108.4N4—N3—N2108.1 (2)
H9A—C9—H9B107.4N3—N4—C6107.9 (3)
C9—C10—C11113.0 (3)C8—N5—C7124.1 (3)
C9—C10—C12108.6 (4)C8—N5—C13119.5 (2)
C11—C10—C12110.6 (4)C7—N5—C13116.3 (2)
C9—C10—H10108.2C8—N6—C5112.1 (3)
C11—C10—H10108.2C8—N7—C9121.7 (3)
C12—C10—H10108.2C8—N7—H7119.2
C10—C11—H11A109.5C9—N7—H7119.2
C10—C11—H11B109.5C1—S1—C388.22 (16)
H11A—C11—H11B109.5
N1—C2—C3—C4179.0 (3)C3—C4—N2—N384.1 (3)
N1—C2—C3—S1−0.4 (4)C5—N2—N3—N4−0.6 (3)
C2—C3—C4—N2−127.6 (3)C4—N2—N3—N4178.7 (3)
S1—C3—C4—N251.7 (4)N2—N3—N4—C60.7 (3)
N2—C5—C6—N40.3 (3)C5—C6—N4—N3−0.6 (4)
N6—C5—C6—N4−179.7 (3)C7—C6—N4—N3179.1 (3)
N2—C5—C6—C7−179.5 (3)N6—C8—N5—C76.6 (5)
N6—C5—C6—C70.5 (5)N7—C8—N5—C7−173.7 (3)
C5—C6—C7—O1−179.3 (3)N6—C8—N5—C13−175.5 (3)
N4—C6—C7—O11.0 (6)N7—C8—N5—C134.2 (4)
C5—C6—C7—N52.1 (4)O1—C7—N5—C8175.8 (3)
N4—C6—C7—N5−177.6 (3)C6—C7—N5—C8−5.5 (4)
N7—C9—C10—C1153.4 (5)O1—C7—N5—C13−2.1 (4)
N7—C9—C10—C12176.6 (3)C6—C7—N5—C13176.7 (3)
C18—C13—C14—C151.1 (5)C18—C13—N5—C8−98.9 (3)
N5—C13—C14—C15−179.5 (3)C14—C13—N5—C881.6 (4)
C13—C14—C15—C16−0.8 (5)C18—C13—N5—C779.0 (4)
C14—C15—C16—C170.0 (6)C14—C13—N5—C7−100.4 (3)
C15—C16—C17—C180.5 (5)N7—C8—N6—C5177.0 (3)
C14—C13—C18—C17−0.5 (5)N5—C8—N6—C5−3.3 (4)
N5—C13—C18—C17180.0 (3)N2—C5—N6—C8179.9 (3)
C16—C17—C18—C13−0.3 (5)C6—C5—N6—C8−0.1 (4)
S1—C1—N1—C20.9 (4)N6—C8—N7—C9−7.2 (5)
Cl1—C1—N1—C2−178.7 (3)N5—C8—N7—C9173.1 (3)
C3—C2—N1—C1−0.3 (4)C10—C9—N7—C888.0 (4)
N6—C5—N2—N3−179.9 (3)N1—C1—S1—C3−1.0 (3)
C6—C5—N2—N30.2 (3)Cl1—C1—S1—C3178.6 (2)
N6—C5—N2—C40.9 (5)C2—C3—S1—C10.7 (3)
C6—C5—N2—C4−179.1 (3)C4—C3—S1—C1−178.8 (3)
C3—C4—N2—C5−96.8 (4)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N7—H7···N1i0.862.282.993 (4)141
Symmetry codes: (i) x−1/2, y+1/2, z.
Table 1
Selected geometric parameters (Å) top
C5—N61.344 (4)C8—N51.397 (4)
C6—N41.377 (4)C9—N71.454 (4)
C7—N51.426 (4)C13—N51.446 (4)
C8—N61.316 (4)N2—N31.376 (3)
C8—N71.349 (4)N3—N41.298 (3)
Table 2
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N7—H7···N1i0.862.282.993 (4)141
Symmetry codes: (i) x−1/2, y+1/2, z.
Acknowledgements top

The authors are grateful to the Natural Science Foundation of China (grant No. 20302002) for financial support, and to Mr Xiang-Gao Meng for the X-ray diffraction analysis.

references
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