With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.61296-22-8,2-Amino-5-bromothiazole monohydrobromide,as a common compound, the synthetic route is as follows.
NEt3 (63.4mL, 455MMOL) was added to a stirred suspension of 5- BROMOTHIAZOL-2-YLAMINE hydrobromide (102. 7g, 379MMOL) in CH2C12 (1. 5L). After LH, TFAA (64.2mL, 455MMOL) was added dropwise at 0 C over 15MIN. The mixture was allowed to warm to 20 C over lh, before being stirred for an additional 2h. H20 (600mL) was added and the resulting precipitate was collected. The aqueous layer of the filtrate was separated and extracted with CHC13 (3 x 300mL). The combined organic extracts were washed with brine, dried (NA2S04), filtered and concentrated. The collected precipitate and residual solid were combined and triturated with ETOAC-N-C6HO4 to give N- (5-BROMOTHIAZOL-2-YL)-2, 2,2-trifluoroacetamide : No.H (CDC13) : 7.45 (s, 1H), 13.05 (br, 1H). N-BULI (253mL of a 1.58M solution in hexanes, 403MMOL) was added dropwise over 50MIN to a stirred solution of the above amide (50. 0G, 183mmol) in anhydrous THF (1.3L) AT-78 C. After 1. 5H, a solution of N-FLUOROBENZENESULFONIMIDE (86. 0G, 275mmol) in anhydrous THF (250mL) was added dropwise over 30min. The mixture was stirred for 3h, before being warmed up TO-30 C. H20 (300mL) was added and the mixture was filtered through a Celite pad. The solid collected and Celite were washed with ET20 (400mL) and H20 (400mL). The organic layer of the filtrate was separated and extracted with water (2 x 400mL). The combined aqueous layers were washed with Et2O (400ML), before being acidified to pH 6.5 with 2M HC1 and extracted with EtOAc (2 x 400mL). The combined organic extracts were washed with H20 (2 x 400mL) and brine, before being dried (MgS04), filtered and concentrated. Column chromatography (EtOAc- N-C6H14, 1: 3 to 1: 2) GAVE N- (5-FLUOROTHIAZOL-2-YL)-2, 2, 2-TRIFLUOROACETAMIDE : & (CDC13) : 7.13 (d, 1H). AcCl (12.6mL, 175MMOL) was added dropwise to a stirred solution of this amide (15.7g, 73MMOL) in MEOH (300mL) at 0 C. The mixture was stirred at 20 C for 30min, heated under reflux for lh, and finally concentrated in vacuo. The residual solid was triturated with THF to give the title compound: I5H (D2O) : 7.00 (d, 1H)., 61296-22-8
The synthetic route of 61296-22-8 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; OSI PHARMACEUTICALS, INC.; WO2004/72066; (2004); A1;,
Thiazole | C3H3NS – PubChem
Thiazole | chemical compound | Britannica