反应详情

102 μL (0.73 mmol) of triethylamine and 117 mg (0.36 mmol) of TBTU were added to a solution of 73.7 mg (0.37 mmol) of 1-tert-butoxycarbonylamino-cyclopropanecarboxylic acid in 6 mL DMF and the mixture was stirred for 5 min at RT. Then 96.6 mg (0.37 mmol) of 4-(2-chloro-4-methoxy-phenoxy)-benzylamine was added and the mixture was stirred overnight at ambient temperature. The reaction mixture was filtered through Alox B, washed with DMF and the filtrate was evaporated down. 10 ml of dichloromethane/trifluoroacetic acid=1/1 were added to the residue and this was shaken for 1 h at RT. The reaction mixture was evaporated down and the residue was purified by chromatography (reversed phase). The corresponding fractions were freeze-dried. 35 mg (0.18 mmol) of 5-(trifluoromethyl)nicotinic acid was dissolved in 2 ml DMF and combined with 52 μL (0.37 mmol) of triethylamine and 59 mg (0.18 mmol) of TBTU and stirred for 10 min at RT. Then the freeze-dried 1-amino-cyclopropanecarboxylic acid-4-(2-chloro-4-methoxy-phenoxy)-benzylamide was added and the mixture was stirred overnight at RT. The reaction mixture was purified directly by chromatography (reversed phase).

1. stirringthe mixture was stirred overnight at ambient temperature
2. filtrationThe reaction mixture was filtered through Alox B
3. washwashed with DMF
4. customthe filtrate was evaporated down
5. addition10 ml of dichloromethane/trifluoroacetic acid=1/1 were added to the residue
6. stirringthis was shaken for 1 h at RT
7. customThe reaction mixture was evaporated down
8. customthe residue was purified by chromatography (reversed phase)
9. customThe corresponding fractions were freeze-dried
10. stirringstirred for 10 min at RT
11. stirringthe mixture was stirred overnight at RT
12. customThe reaction mixture was purified directly by chromatography (reversed phase)