反应详情

In a 25 mL round-bottomed flask, 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-2-(trifluoromethyl)benzoic acid (42 mg, 64.2 μmol, Eq: 1.00) was combined with DMF (2.50 ml) to give a colorless solution. HATU (36.6 mg, 96.3 μmol, Eq: 1.5) and DIPEA (41.5 mg, 56.0 μl, 321 μmol, Eq: 5) were added. The reaction was stirred for 5 minutes and ammonia hydrochloride (34.3 mg, 642 μmol, Eq: 10) was added. The reaction mixture was stirred for overnight. The reaction mixture was poured into 10 mL of H2O and extracted with EtOAc (3×10 mL). The organic layers were combined, washed with H2O (1×10 mL), saturated NaCl (1×10 mL), dried over Na2SO4 and concentrated in vacuum. The crude material was purified by preparative HPLC (65-100% ACETONITRILE/water). The fractions were combined and freeze dried and triturated with CH2Cl2/hexanes to give a white foam (12 mg, 26% yield). (ES+) m/z Calcd: [(M+H)+]: 653. found: 653.

1. customto give a colorless solution
2. stirringThe reaction mixture was stirred for overnight
3. extractionextracted with EtOAc (3×10 mL)
4. washwashed with H2O (1×10 mL), saturated NaCl (1×10 mL)
5. dry with materialdried over Na2SO4
6. concentrationconcentrated in vacuum
7. customThe crude material was purified by preparative HPLC (65-100% ACETONITRILE/water)
8. customfreeze dried
9. customtriturated with CH2Cl2/hexanes