Trimethyl orthoformate → HCID 86646360, compound

Participants

Reaction Conditions

Reaction Steps

Methyl 5-({5-[(4-methyl-1-piperazinyl)methyl]-2-nitrophenyl}amino)-3-({(1R)-1-[2-(trifluoromethyl)phenyl]ethyl}oxy)-2-thiophenecarboxylate dihydrochloride (50.0 g, 76.8 mmol) was suspended in MeOH (100 mL) and trimethylorthoformate (200 mL) and stirred for half an hour. Ammonium formate (30.0 g) and 10% Pd/C (25 g, 15.4 mol %) were added and the mixture was heated to 35° C. The temperature was increased to 60° C. over 6 hours and then held at 60° C. overnight before filtering through fibreglass paper, washing with EtOAc (300 mL). The filtrate was washed with aqueous sodium hydroxide (2 M, 250 mL) and then brine (2×150 mL). A solution of HCl (4 M) was prepared by dropwise addition of acetyl chloride (16.4 mL) to MeOH (41.3 mL), cooled with an ice-bath. This solution was warmed to room temperature and then added dropwise over half an hour to the reaction mixture at 45° C. The mixture was stirred for a further half an hour at 45° C., cooled to room temperature over 1 hour and then cooled in an ice-bath for a further hour, filtered, washing with EtOAc (150 mL) and then dried under reduced pressure to give the title compound (42.7 g, 83% th) as off-white crystalline solid.

Provenance & Evidence