Ethyl orthoformate → HCID 18651641, compound

Participants

Reaction Conditions

Reaction Steps

Under nitrogen atmosphere, N-{4-chloro-5-formamido-6-[(1R,4S)-4-(hydroxymethyl)cyclopent-2-enylamino]pyrimidin-2-yl}isobutyramide (20.0 g, 56.53 mmol) was dissolved in an anhydrous solution of HCl/isopropanol 2M (170 ml, 339.17 mmol). The mixture was heated at 40-42° C. for 2 h. The resulting solution was cooled to 8-10° C., then triethyl orthoformate (28.2 ml, 169.59 mmol) was added and the reaction mixture was stirred at the same temperature for 2 h. NaHCO3 (28.50 g, 339.17 mmol) was added slowly, stirred 30 min and the salts were filtered off. To the resulting clear solution, NaHCO3 (4.75 g, 56.53 mmol) and cyclopropylamine (19.6 ml, 282.65 mmol) were added, the mixture was refluxed for 1 h and the salts were filtered off. The solution was evaporated and the syrup was dissolved in hot isopropanol (200 ml). This mixture was cooled to 0-2° C. and the resulting slurry filtered off. The solid was dried under vacuum at 30° C. There was obtained 14.42 g (72%) of (−)-N-{6-(cyclopropylamino)-9-[(1R,4S)-4-(hydroxymethyl)cyclopent-2-enyl]-9H-purin-2-yl}isobutyramide as a white powder. HPLC analysis: 94.4%+4.0% Abacavir.

Provenance & Evidence