反应详情

To a solution of 200 mg (0.73 mmol) of dimethyl 2-[1-(4-aminophenyl)but-2-ynyl]-malonate, 251 mg (2.18 mmol) of N-ethylmorpholine, 122 mg (0.8 mmol) of HOBt hydrate and 124 mg (0.80 mmol) of EDAC in 5 ml of DMF was added a solution of 213 mg (0.73 mmol) of 2-(4-bromo-2-chlorophenoxy)-2-methylpropionic acid in 3 ml of DMF. After 18 h at room temperature, another 1.1 equivalents each of N-ethylmorpholine and HOBt hydrate were added. After 72 h, the reaction mixture was concentrated completely and separated by means of preparative HPLC (Merck Hibar Purospher Star RP-18e 10 μm 25×250 mm; A: H2O+0.05% TFA; B: ACN+0.05% TFA; flow rate: 50 ml/min; in 10 minutes 10% B→80% B; in 5 minutes 80% B→90% B). The product fractions were freeze-dried to obtain 180 mg (45%) of dimethyl 2-(1-{-[2-(4-bromo-2-chlorophenoxy)-2-methylpropionylamino]phenyl}but-2-ynyl)malonate.

1. waitAfter 72 h
2. concentrationthe reaction mixture was concentrated completely
3. customseparated by means of preparative HPLC (Merck Hibar Purospher Star RP-18e 10 μm 25×250 mm
4. waitin 10 minutes 10% B→80% B
5. waitin 5 minutes 80% B→90% B)
6. customThe product fractions were freeze-dried