反应详情

Following the procedure for the synthesis of Example 40 Step 3 (without DIEA), tert-butyl 3-[N-((1R)-2-{4-[2-({2-[(tert-butoxy)carbonylamino]ethyl}amino)phenyl]-piperazinyl}-1-[(4-chlorophenyl)methyl]-2-oxoethyl)-carbamoyl](3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate was prepared from tert-butyl 3-(N-{(1R)-2-[4-(2-aminophenyl)piperazinyl]-1-[(4-chlorophenyl)-methyl]-2-oxoethyl}carbamoyl)(3S)-1,2,3,4-tetrahydro-isoquinoline-2-carboxylate (Preparation IX) (630 mg, 1.0 mmol) in 2 mL of ClCH2CH2Cl, tert-butyl-N-(2-oxoethyl)carbamate (179 mg, 1.126 mmol) (Aldrich) in ClCH2CH2Cl (10 mL), and NaBH(OAc)3 (330 mg, 1.557 mmol) (Aldrich). The crude was purified by flash chromatography (SiO2, 2:1 hexane:EtOAc) to afford the desired compound (578 mg). MS (ESI, pos. ion) m/z: 761 (M+H), (ESI, neg. ion) m/z: 759 (M−H). Calc'd for C4lH53ClN6O6: 761.35. Anal. Calc'd for C41H53ClN6O6-0.5 C4H8O2-0.5 H2O: C, 63.42; H, 7.18; N, 10.32; Cl, 4.35. Found C, 62.96 (±0.46); H, 7.14; N, 10.26; Cl, 4.06.

1. customThe crude was purified by flash chromatography (SiO2, 2:1 hexane:EtOAc)