Acetic Anhydride → Acetic acid 2-{3-[(R)-{4-[amino(2-methylallyloxycarbonylimino)methyl]phenylamino}-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]-2-fluoro-5-methoxyphenoxy}ethyl ester

Participants

Reaction Steps

At room temperature, 4-{[(R)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl](5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]amino}benzamidine hydrochloride (5.058 g, 9.42 mmol) was dissolved in dimethyl sulfoxide (15 mL), and potassium carbonate (3.91 g, 28.3 mmol) was added thereto. To the resulting mixture, 2-methyl-allyl phenyl carbonate (1.81 g, 9.42 mmol) was added under stirring at room temperature, and the resulting mixture was stirred for 18 hours. Thereafter, 4-dimethylaminopyridine (57.5 mg, 0.471 mmol) and acetic anhydride (2.23 mL, 23.6 mmol) were added to the reaction solution, and the resulting mixture was stirred for 1.5 hours. Further, acetic anhydride (0.223 mL, 2.36 mmol) was added to the mixture, and the resulting mixture was stirred for 2 hours. To the reaction solution, tetrahydrofuran (20 mL) and ethyl acetate (40 mL) were added, and 5% aqueous sodium hydrogen carbonate solution (50 g) was added to quench the reaction, after which the layers were separated at 50° C. Furthermore, the aqueous layer was extracted twice with a mixture of tetrahydrofuran (20 mL) and ethyl acetate (40 mL). The organic layer was combined, washed twice with 5% aqueous sodium hydrogen carbonate solution (25 g) and once with 5% saline, and then concentrated under reduced pressure. Acetone (30 mL) was added to the residue obtained, and the resulting mixture was stirred at room temperature for 3 hours, after which tert-butyl methyl ether (25 mL) was added to the mixture, and the resulting mixture was stirred at 4° C. for 16 hours. The precipitate was filtered and dried to obtain the captioned compound (3.74 g) as a pale yellow solid.

Provenance & Evidence