N-(2-Chloro-6-methylphenyl)-2-[(6-chloro-2-methyl-4-pyrimidinyl)amino]-5-thiazolecarboxamide Chemical Properties

Melting point:

333-335°C

Boiling point:

566.95° C (Predicted)

Density 

1.516±0.06 g/cm3(Predicted)

refractive index 

n20D 1.72 (Predicted)

storage temp. 

Inert atmosphere,2-8°C

solubility 

DMSO (Slightly)

form 

Solid

pka

10.92±0.70(Predicted)

color 

Pale Yellow

Water Solubility 

Slightly soluble in water

InChI

InChI=1S/C16H13Cl2N5OS/c1-8-4-3-5-10(17)14(8)23-15(24)11-7-19-16(25-11)22-13-6-12(18)20-9(2)21-13/h3-7H,1-2H3,(H,23,24)(H,19,20,21,22)

InChIKey

LMXUWARKUIELGT-UHFFFAOYSA-N

SMILES

S1C(C(NC2=C(C)C=CC=C2Cl)=O)=CN=C1NC1C=C(Cl)N=C(C)N=1

CAS DataBase Reference

302964-08-5(CAS DataBase Reference)

Safety Information

HS Code 

2933399990

N-(2-Chloro-6-methylphenyl)-2-[(6-chloro-2-methyl-4-pyrimidinyl)amino]-5-thiazolecarboxamide Usage And Synthesis

Description

N-(2-Chloro-6-methylphenyl)-2-[(6-chloro-2-methyl-4-pyrimidinyl)amino]-5-thiazolecarboxamide is a pharmaceutical intermediate compound used as a synthetic intermediate for dasatinib. Dasatinib is a targeted anticancer drug used to treat chronic myeloid leukaemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL). It is also a receptor and non-receptor Tyk (tyrosine kinase) inhibitor, which plays an important role in certain cancers and fibrotic diseases.

Chemical Properties

Pale Yellow Solid

Uses

Dasatinib intermediate. A protein tyrosine kinase inhibitor.

Synthesis

General procedure for the synthesis of N-(2-chloro-6-methylphenyl)-2-[(6-chloro-2-methyl-4-pyrimidinyl)amino]-5-thiazolecarboxamide from 4,6-dichloro-2-methylpyrimidine and 2-amino-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide: To 80 mL of tetrahydrofuran, cooled to -25 °C, was added 8.73 g of potassium hydride (30 wt%, 65.38 mmol) and stirred for 10 minutes; 5.00 g of 2-amino-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide was slowly added and the temperature was maintained at -25 °C; followed by the addition of 3.65 g of 4,6-dichloro-2-methylpyrimidine to a tetrahydrofuran solution (7 mL), the temperature was maintained stable and the reaction mixture was stirred for 4 hours at -10 °C. After completion of the reaction, 1 M hydrochloric acid was slowly added to quench the reaction, pH was adjusted to 6, the temperature was controlled at 0-5 °C for 2 h. Crystallization was carried out by centrifugation and washed with tetrahydrofuran. The crude product was obtained as 7.27 g in 98.7% yield and 99.95% purity (HPLC) with a maximum single heterogeneous content of 0.03%.

References

[1] Patent: CN104788445, 2017, B. Location in patent: Paragraph 0016; 0026; 0027; 0029; 0031; 0033; 0035; 0037
[2] Science China Chemistry, 2014, vol. 57, # 6, p. 823 - 832
[3] Synthetic Communications, 2017, vol. 47, # 17, p. 1610 - 1621
[4] Patent: WO2005/77945, 2005, A2. Location in patent: Page/Page column 51-52
[5] Arkivoc, 2010, vol. 2010, # 6, p. 32 - 38

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