4-Methylmorpholine → rac-8-[(2,6-Difluorobenzyl)oxy]-2-methyl-N-(1,1,1-trifluoro-3-hydroxypropan-2-yl)imidazo[1,2-a]pyridine-3-carboxamide

Participants

Reaction Steps

50 mg (0.16 mmol) of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid, 55 mg (0.17 mmol) of (benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate (TBTU) and 79 mg (0.79 mmol) of 4-methylmorpholine were initially charged in 1.0 ml of dichloromethane. After 10 min at RT, 28 mg (0.17 mmol) of 2-amino-4,4,4-trifluorobutan-1-ol were added and the mixture was stirred at room temperature overnight. 1 ml of DMF and 50 mg (0.39 mmol) of 2-amino-4,4,4-trifluorobutan-1-ol were then added, and the mixture was stirred at 50° C. for 8 h. Another 50 mg (0.39 mmol) of 2-amino-4,4,4-trifluorobutan-1-ol were added, and the mixture was stirred in a microwave at 80° C. for 0.5 h. Another 50 mg (0.39 mmol) of 2-amino-4,4,4-trifluorobutan-1-ol were then added, and the mixture was stirred in a microwave at 80° C. for 1 h. The reaction solution was concentrated and purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). All product-containing fractions were combined and concentrated. The residue was dissolved in dichloromethane and washed with saturated aqueous sodium bicarbonate solution. This gave 17 mg of the target compound (25% of theory, purity 100%).

Provenance & Evidence