反应详情

100 mg (0.31 mmol) of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid, 111 mg (0.35 mmol) of (benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate (TBTU) and 159 mg (1.57 mmol) of 4-methylmorpholine were initially charged in 2.0 ml of dichloromethane. After 10 min at RT, 142 mg (0.35 mmol) of 2-amino-2-(3,4-difluorophenyl)-ethanol were added and the mixture was stirred at room temperature overnight. The reaction solution was concentrated, and acetonitrile/methanol/water was added. A solid precipitated out, and this solid was filtered off and purified by chromatography on silica gel (mobile phase: dichloromethane:THF=10:1→5:1). The combined product fractions were concentrated and then triturated with acetonitrile, and the solid was filtered off and washed with methanol. This gave 39 mg of the target compound (26% of theory, purity 95%). After some time, the filtrate produced more solid; this gave another 5 mg of the target compound (3.3% of theory, purity 99%).

1. concentrationThe reaction solution was concentrated
2. additionacetonitrile/methanol/water was added
3. customA solid precipitated out
4. filtrationthis solid was filtered off
5. custompurified by chromatography on silica gel (mobile phase: dichloromethane:THF=10:1→5:1)
6. concentrationThe combined product fractions were concentrated
7. customtriturated with acetonitrile
8. filtrationthe solid was filtered off
9. washwashed with methanol
10. customAfter some time, the filtrate produced more solid