反应详情

A solution of (R)-4-nitrophenyl 1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (50 mg, 113 μmol, example 88) and 4-amino-3-fluorobenzonitrile (17 mg, 124 mop in MeCN (0.7 mL) was subjected to a microwave irradiation at 120° C. for 15 min and at 150° C. for 15 min. Then, NaH (60% dispersion in mineral oil, 20 mg) was added and the mixture was then stirred at RT for overnight. Then, H2O (1.0 mL) was added and the mixture was extracted with EtOAc (2×1.5 mL). The combined organic extracts were dried over MgSO4 and concentrated. The residue was then dissolved in a solution of DMSO and MeOH (1:1, 0.1 mL). The solution mixture was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA) to give a desired product, which was then dissolved in MeOH (1.0 mL). The solution was then washed through PL-HCO3 MP-resin and the resin was washed with MeOH (2×0.5 mL). The combined washings were concentrated and dried under vacuum to give the title compound as a colorless solid. MS (ESI, positive ion) m/z: 440 (M+H).

1. extractionthe mixture was extracted with EtOAc (2×1.5 mL)
2. dry with materialThe combined organic extracts were dried over MgSO4
3. concentrationconcentrated
4. dissolutionThe residue was then dissolved in a solution of DMSO and MeOH (1:1, 0.1 mL)
5. customThe solution mixture was then purified by preparative HPLC (0%-100% MeCN 0.1% TFA/H2O 0.1% TFA)