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Acta Crystallogr Sect E Struct Rep Online. 2010 September 1; 66(Pt 9): o2343.
Published online 2010 August 18. doi:  10.1107/S1600536810032277
PMCID: PMC3007983

Methyl 2-(tert-but­oxy­carbonyl­amino)-1,3-thia­zole-5-carboxyl­ate

Abstract

The title compound, C10H14N2O4S, was synthesized by the reaction of methyl 2-amino­thia­zole-5-carboxyl­ate and di-tert-butyl carbonate. In this structure, the thia­zole ring is planar (mean deviation = 0.0011 Å). Two weak intra­molecular C—H(...)O hydrogen bonds are formed between two of the methyl groups and one carbonyl O atom, resulting in the formation of two twisted six-membered rings. Inter­molecular N—H(...)N hydrogen bonds link the mol­ecules to form centrosymmetric dimeric units, and the hydrogen-bond scheme is completed by inter­molecular C—H(...)O contacts.

Related literature

For information on the use of the title compound in the synthesis of dasatinib [systematic name: N-(2-chloro-6-methyl­phenyl)-2-({6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methyl­pyrimidin-4-yl}amino)-5-thiazolecarboxamide], see: Lombardo et al. (2004 [triangle]). For information on the effectiveness of dasatinib in imatinib-resistant Bcr–Abl kinase domain mutants, see: Shah et al. (2004 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o2343-scheme1.jpg

Experimental

Crystal data

  • C10H14N2O4S
  • M r = 258.29
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2343-efi1.jpg
  • a = 7.0700 (14) Å
  • b = 9.2580 (19) Å
  • c = 10.708 (2) Å
  • α = 70.10 (3)°
  • β = 79.67 (3)°
  • γ = 79.08 (3)°
  • V = 642.1 (2) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.26 mm−1
  • T = 293 K
  • 0.30 × 0.10 × 0.10 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: ψ scan (North et al., 1968 [triangle]) T min = 0.927, T max = 0.975
  • 2543 measured reflections
  • 2338 independent reflections
  • 1975 reflections with I > 2σ(I)
  • R int = 0.014
  • 3 standard reflections every 200 reflections intensity decay: 1%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.047
  • wR(F 2) = 0.142
  • S = 1.01
  • 2338 reflections
  • 154 parameters
  • H-atom parameters constrained
  • Δρmax = 0.22 e Å−3
  • Δρmin = −0.36 e Å−3

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1989 [triangle]); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810032277/bh2305sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810032277/bh2305Isup2.hkl

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

Acknowledgments

The authors thank Professor Hua-qin Wang (Nanjing University) for carrying out the X-ray crystallographic analysis.

supplementary crystallographic information

Comment

Methyl 2-((tert-butoxycarbonyl)amino)thiazole-5-carboxylate is an important intermediate compound in research on synthesizing Dasatinib (Lombardo et al., 2004). Dasatinib is a high affinity dual Src/Abl and c-Kit inhibitor that has been recently approved for all categories of imatinib-refractory chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). Dasatinib is also effective in many imatinib resistant Bcr–Abl kinase domain mutants (Shah et al., 2004).

We report here the crystal structure of the title compound, (I). The molecular structure of (I) is shown in Fig. 1. Ring A (S/C5/N1/C4/C3) is a planar five-membered ring with a r.m.s. deviation of 0.0011 Å. In this plane, atoms S, C5, N1, C4 and C3 deviate from the mean plane by less than 0.002 Å. The intramolecular C—H···O hydrogen bonds (Table 1) result in the formation of two twisty six-membered rings B (O3/C6/O4/C7/C8/H8A) and C (O3/C6/O4/C7/C10/H10A). In the crystal structure, intermolecular N—H···N hydrogen bonds (Table 1) link the molecules to form dimeric units (Fig. 2), stabilizing the crystal structure. The hydrogen bonds scheme is completed by intermolecular C—H···O contacts.

Experimental

Methyl 2-aminothiazole-5-carboxylate (10 mmol), di-tert-butyl carbonate (12 mmol) and 4-dimethylamino pyridine (0.66 mmol) were added in THF (30 ml), stirred and refluxed under a nitrogen atmosphere for 10 h. The reaction mixture was left to cool to room temperature, precipitated, filtered, and the filter cake was crystallized from ethanol to give pure compound (I). Crystals of (I) suitable for X-ray diffraction were obtained by slow evaporation of an ethanol solution.

Refinement

All H atoms were positioned geometrically, with C—H = 0.96 and 0.93 Å for methyl and aromatic H atoms, respectively, and N—H = 0.86 Å. All H atoms were constrained to ride on their parent atoms, with Uiso(H) = xUeq(carrier atom), where x = 1.5 for methyl H atoms and x = 1.2 for all other H atoms.

Figures

Fig. 1.
A view of the molecular structure of (I). Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate intramolecular C—H···O hydrogen bonds.
Fig. 2.
A packing diagram for (I). Dashed lines indicate C—H···N and C—H···O hydrogen bonds.

Crystal data

C10H14N2O4SZ = 2
Mr = 258.29F(000) = 272
Triclinic, P1Dx = 1.336 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 7.0700 (14) ÅCell parameters from 25 reflections
b = 9.2580 (19) Åθ = 10–13°
c = 10.708 (2) ŵ = 0.26 mm1
α = 70.10 (3)°T = 293 K
β = 79.67 (3)°Block, colourless
γ = 79.08 (3)°0.30 × 0.10 × 0.10 mm
V = 642.1 (2) Å3

Data collection

Enraf–Nonius CAD-4 diffractometer1975 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.014
graphiteθmax = 25.3°, θmin = 2.0°
ω/2θ scansh = 0→8
Absorption correction: ψ scan (North et al., 1968)k = −10→11
Tmin = 0.927, Tmax = 0.975l = −12→12
2543 measured reflections3 standard reflections every 200 reflections
2338 independent reflections intensity decay: 1%

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)] = 0.047Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.142H-atom parameters constrained
S = 1.01w = 1/[σ2(Fo2) + (0.1P)2 + 0.077P] where P = (Fo2 + 2Fc2)/3
2338 reflections(Δ/σ)max < 0.001
154 parametersΔρmax = 0.22 e Å3
0 restraintsΔρmin = −0.36 e Å3
0 constraints

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
S0.31065 (8)0.77835 (6)0.78035 (6)0.0496 (2)
N10.1959 (3)1.0086 (2)0.58090 (19)0.0477 (5)
O10.6194 (3)0.8268 (2)0.89511 (19)0.0668 (5)
C10.7656 (4)0.8233 (4)0.9752 (3)0.0845 (10)
H1B0.78150.72391.04300.127*
H1C0.72580.90291.01680.127*
H1D0.88660.84060.91900.127*
N20.0259 (3)0.7987 (2)0.63197 (18)0.0476 (5)
H2A−0.04540.85110.56980.057*
O20.6587 (4)1.0667 (2)0.7674 (3)0.1004 (8)
C20.5780 (3)0.9562 (3)0.7965 (3)0.0538 (6)
O30.0857 (3)0.56934 (19)0.79484 (18)0.0637 (5)
C30.4211 (3)0.9438 (2)0.7294 (2)0.0466 (5)
O4−0.1471 (2)0.61245 (16)0.65983 (15)0.0486 (4)
C40.3422 (3)1.0503 (2)0.6244 (2)0.0504 (6)
H4A0.38451.14670.58350.061*
C50.1664 (3)0.8678 (2)0.6549 (2)0.0413 (5)
C6−0.0051 (3)0.6494 (2)0.7045 (2)0.0462 (5)
C7−0.2028 (3)0.4528 (2)0.7162 (2)0.0471 (5)
C8−0.2827 (4)0.4215 (3)0.8624 (2)0.0627 (7)
H8A−0.18060.41650.91260.094*
H8B−0.33380.32460.89540.094*
H8C−0.38420.50350.87180.094*
C9−0.3586 (4)0.4627 (3)0.6324 (3)0.0622 (7)
H9A−0.30350.48300.54040.093*
H9B−0.46040.54510.64030.093*
H9C−0.41070.36630.66330.093*
C10−0.0294 (4)0.3355 (3)0.6947 (3)0.0594 (6)
H10A0.06730.33130.74890.089*
H10B0.02410.36570.60210.089*
H10C−0.06990.23510.71970.089*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S0.0506 (4)0.0442 (3)0.0525 (4)−0.0135 (2)−0.0243 (3)−0.0006 (2)
N10.0485 (10)0.0378 (9)0.0545 (10)−0.0097 (8)−0.0187 (8)−0.0035 (8)
O10.0607 (11)0.0730 (12)0.0673 (11)−0.0191 (9)−0.0341 (9)−0.0046 (9)
C10.0636 (17)0.120 (3)0.081 (2)−0.0089 (17)−0.0399 (16)−0.0318 (19)
N20.0527 (11)0.0383 (9)0.0512 (10)−0.0130 (8)−0.0265 (9)0.0002 (8)
O20.0982 (16)0.0674 (13)0.144 (2)−0.0372 (12)−0.0668 (16)−0.0038 (13)
C20.0439 (12)0.0543 (14)0.0684 (15)−0.0107 (10)−0.0157 (11)−0.0196 (12)
O30.0749 (11)0.0483 (9)0.0655 (10)−0.0212 (8)−0.0409 (9)0.0079 (8)
C30.0406 (11)0.0447 (12)0.0558 (13)−0.0098 (9)−0.0144 (10)−0.0114 (10)
O40.0564 (9)0.0403 (8)0.0488 (9)−0.0159 (7)−0.0232 (7)−0.0005 (6)
C40.0496 (12)0.0383 (11)0.0628 (14)−0.0130 (9)−0.0154 (11)−0.0074 (10)
C50.0424 (11)0.0377 (10)0.0426 (11)−0.0066 (8)−0.0124 (9)−0.0069 (8)
C60.0519 (12)0.0406 (11)0.0466 (11)−0.0122 (9)−0.0198 (10)−0.0046 (9)
C70.0482 (12)0.0409 (11)0.0506 (12)−0.0162 (9)−0.0134 (10)−0.0035 (9)
C80.0643 (15)0.0627 (15)0.0529 (14)−0.0171 (12)−0.0054 (12)−0.0043 (12)
C90.0623 (15)0.0575 (14)0.0714 (16)−0.0204 (12)−0.0261 (13)−0.0107 (12)
C100.0605 (14)0.0496 (13)0.0689 (16)−0.0116 (11)−0.0141 (12)−0.0146 (11)

Geometric parameters (Å, °)

S—C51.716 (2)O4—C61.329 (3)
S—C31.728 (2)O4—C71.494 (2)
N1—C51.309 (3)C4—H4A0.9300
N1—C41.372 (3)C7—C91.512 (3)
O1—C21.324 (3)C7—C81.513 (3)
O1—C11.446 (3)C7—C101.517 (3)
C1—H1B0.9600C8—H8A0.9600
C1—H1C0.9600C8—H8B0.9600
C1—H1D0.9600C8—H8C0.9600
N2—C61.373 (3)C9—H9A0.9600
N2—C51.375 (3)C9—H9B0.9600
N2—H2A0.8600C9—H9C0.9600
O2—C21.187 (3)C10—H10A0.9600
C2—C31.466 (3)C10—H10B0.9600
O3—C61.205 (3)C10—H10C0.9600
C3—C41.345 (3)
C5—S—C388.29 (10)O3—C6—N2122.9 (2)
C5—N1—C4109.33 (19)O4—C6—N2109.62 (17)
C2—O1—C1117.7 (2)O4—C7—C9102.10 (17)
O1—C1—H1B109.5O4—C7—C8109.55 (19)
O1—C1—H1C109.5C9—C7—C8111.5 (2)
H1B—C1—H1C109.5O4—C7—C10109.70 (18)
O1—C1—H1D109.5C9—C7—C10111.0 (2)
H1B—C1—H1D109.5C8—C7—C10112.4 (2)
H1C—C1—H1D109.5C7—C8—H8A109.5
C6—N2—C5122.54 (18)C7—C8—H8B109.5
C6—N2—H2A118.7H8A—C8—H8B109.5
C5—N2—H2A118.7C7—C8—H8C109.5
O2—C2—O1123.7 (2)H8A—C8—H8C109.5
O2—C2—C3125.2 (2)H8B—C8—H8C109.5
O1—C2—C3111.0 (2)C7—C9—H9A109.5
C4—C3—C2128.1 (2)C7—C9—H9B109.5
C4—C3—S110.13 (16)H9A—C9—H9B109.5
C2—C3—S121.78 (17)C7—C9—H9C109.5
C6—O4—C7120.74 (16)H9A—C9—H9C109.5
C3—C4—N1116.2 (2)H9B—C9—H9C109.5
C3—C4—H4A121.9C7—C10—H10A109.5
N1—C4—H4A121.9C7—C10—H10B109.5
N1—C5—N2120.82 (19)H10A—C10—H10B109.5
N1—C5—S116.08 (16)C7—C10—H10C109.5
N2—C5—S123.10 (15)H10A—C10—H10C109.5
O3—C6—O4127.5 (2)H10B—C10—H10C109.5
C1—O1—C2—O22.8 (4)C4—N1—C5—S0.3 (3)
C1—O1—C2—C3−177.2 (2)C6—N2—C5—N1177.8 (2)
O2—C2—C3—C41.0 (5)C6—N2—C5—S−2.8 (3)
O1—C2—C3—C4−178.9 (2)C3—S—C5—N1−0.13 (18)
O2—C2—C3—S−179.3 (2)C3—S—C5—N2−179.6 (2)
O1—C2—C3—S0.7 (3)C7—O4—C6—O3−4.2 (4)
C5—S—C3—C4−0.09 (18)C7—O4—C6—N2176.44 (18)
C5—S—C3—C2−179.8 (2)C5—N2—C6—O31.5 (4)
C2—C3—C4—N1−180.0 (2)C5—N2—C6—O4−179.13 (19)
S—C3—C4—N10.3 (3)C6—O4—C7—C9−177.3 (2)
C5—N1—C4—C3−0.4 (3)C6—O4—C7—C864.4 (3)
C4—N1—C5—N2179.8 (2)C6—O4—C7—C10−59.4 (3)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C8—H8A···O30.962.473.030 (4)117.
C10—H10A···O30.962.453.010 (4)117.
N2—H2A···N1i0.862.022.879 (3)174.
C9—H9C···O2ii0.962.603.440 (4)146.
C10—H10C···O2ii0.962.573.436 (4)150.

Symmetry codes: (i) −x, −y+2, −z+1; (ii) x−1, y−1, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BH2305).

References

  • Enraf–Nonius (1989). CAD-4 Software Enraf–Nonius, Delft, The Netherlands.
  • Harms, K. & Wocadlo, S. (1995). CAD-4 EXPRESS University of Marburg, Germany.
  • Lombardo, L. J. et al. (2004). J. Med. Chem.47, 6658–6661. [PubMed]
  • North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.
  • Shah, N. P., Tran, C., Lee, F. Y., Chen, P., Norris, D. & Sawyers, C. L. (2004). Science, 305, 399–402. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography