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

Kang An; Jiannin Guan; Pen Yu; Hao Yang; Rong Wan

doi:10.1107/S1600536810032277

. 2010 Aug 18;66(Pt 9):o2343. doi: 10.1107/S1600536810032277

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

Kang An ^a, Jiannin Guan ^a, Pen Yu ^a, Hao Yang ^b, Rong Wan ^a,^*

PMCID: PMC3007983 PMID: 21588688

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 ▶). For information on the effectiveness of dasatinib in imatinib-resistant Bcr–Abl kinase domain mutants, see: Shah et al. (2004 ▶).

Experimental

Crystal data

C₁₀H₁₄N₂O₄S
M _r = 258.29
Triclinic,
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 ▶) 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
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.36 e Å⁻³

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1989 ▶); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995 ▶); 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: SHELXL97.

Supplementary Material

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

e-66-o2343-sup1.cif^{(16.3KB, cif)}

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

e-66-o2343-Isup2.hkl^{(114.9KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C8—H8A⋯O3	0.96	2.47	3.030 (4)	117
C10—H10A⋯O3	0.96	2.45	3.010 (4)	117
N2—H2A⋯N1ⁱ	0.86	2.02	2.879 (3)	174
C9—H9C⋯O2ⁱⁱ	0.96	2.60	3.440 (4)	146
C10—H10C⋯O2ⁱⁱ	0.96	2.57	3.436 (4)	150

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Symmetry codes: (i) Inline graphic ; (ii) .

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.