反应详情

1-(Cyclobutyl)-hexahydro-1H-1,4-diazepine dihydrochloride (D4) (0.15 g) was stirred with diethylaminomethyl polystyrene (1.0 g), HOBT (0.045 g), 4′-cyano-4-biphenylcarboxylic acid (0.16 g) in DCM (5 ml). EDC (0.16 g) was then added and the reaction was stirred at rt for 16 h. The polymer supported base was filtered off and the filtrate was diluted with DCM (10 ml) and washed with saturated sodium hydrogen carbonate (2×15 ml). The organic layer was then loaded directly onto a silica column eluting with 0-10% MeOH (containing 10% 0.880 ammonia solution)/DCM. The isolated free base product was dissolved in DCM (5 ml) and treated with excess 1N HCl/diethyl ether solution (1 ml) and stirred for 10 min.

1. filtrationwas filtered off
2. additionthe filtrate was diluted with DCM (10 ml)
3. washwashed with saturated sodium hydrogen carbonate (2×15 ml)
4. washeluting with 0-10% MeOH (containing 10% 0.880 ammonia solution)/DCM
5. dissolutionThe isolated free base product was dissolved in DCM (5 ml)
6. additiontreated with excess 1N HCl/diethyl ether solution (1 ml)
7. stirringstirred for 10 min.