In the chemical reaction process,reaction time,type of solvent,can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product.An updated downstream synthesis route of 302964-08-5 as follows., 302964-08-5
62.5 mL of 3-methylbutan-l-ol was charged into 4 necked RBF at ~ 25 C. 2.5 g of N-(2-chloro-6-methylphenyl)-2-[6-chloro-2-methyl-4-pyrimidinyl) amino]-5-thiazole carboxamide and 4.12 g of 1-(3-Hydroxy)ethylpiperazine were added to the reaction mixture. The reaction mass was stirred for ~ 15 mins and then the temperature of reaction mass was raised to 135 C. After stirring the heated reaction mass (along with continuous reaction monitoring), the reaction mass was slowly cooled to 25 C, in 2 h. The cooled reaction mass was then stirred for 5 h, filtered and washed with 5.0 mL 3-methylbutan-l-ol. The material obtained after washing was suck dried for 15 min. The partially wet material obtained above was charged into a RBF and 48.75 mL 3- methylbutan-l -ol, 73 mg Diisopropylethylamine (DIPEA) and 70 mg 2-bromo ethanol were added to the reaction mixture. The reaction mixture was then heated to ~80C, wherein stirring was performed for 12 h. After stirring, the reaction mass was allowed to slowly cool down to -25 C, wherein it was again stirred for 1 h. Then the reaction mass was filtered and washed with 6.5 mL of 3-methylbutan-l-ol. The wet material obtained was unloaded, air dried for 30 min and then vacuum dried for 10 h at 65 C. The material was then allowed to cool down to 25 C and unloaded to obtain 3.0 g crystalline Form-SDI of Dasatinib having XRPD pattern according to Fig-1 , IR spectrum according to Fig-2 and DSC pattern according to Fig- 3. Yield: 83 % % purity (By HPLC): 99.42 % 1H NMR (400 MHz, DMSO) delta 11.39 (s, 1H), 9.8 (s, 1H), 8.22 (s, 1H), 7.4 (dd, 2H), 7.2 (m, 1H), 6.04 (s, 1H), 4.4 (t, 1H), 3.4 (m, 6H), 2.44 (m, 3H), 2.4 (m, 3H), 2.41 (s, 3H), 2.2 (s, 3H), 1.6 (sep, 1H), 1.3 (q, 2H), 0.85 (d, 6H).
The chemical industry reduces the impact on the environment during synthesis 302964-08-5, I believe this compound will play a more active role in future production and life.
Reference:
Patent; SHILPA MEDICARE LIMITED; SRIRAM, Rampalli; PRADEEP, Pothana; SURESH, Garbapu; PRASHANT, Purohit; AKSHAY KANT, Chaturvedi; WO2015/68055; (2015); A1;,
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