反应详情

The compound (1S,2S)-(1-{[benzyloxycarbonyl-(2,4-dimethyl-benzyl)-amino]-methyl}-2-hydroxy-pentyl)-carbamic acid tert-butyl ester (515 mg, 1.06 mmol) was dissolved in CH2Cl2 (12 mL) and treated with TFA (4 mL). The solution was stirred for 3 h and then concentrated in vacuo. The residue was dissolved in benzene and concentrated in vacuo; this procedure was repeated. The resultant amine was dissolved in 15 mL of 2:1 CH2Cl2/DMF. The resultant solution was charged sequentially with N-(3-tert-butoxycarbonylamino-5-trifluoromethyl-phenyl)-malonamic acid (400 mg, 1.1 mmol, see examples 8 and 1), N,N-diisopropylethylamine (0.96 mL, 5.5 mmol) and HATU (504 mg, 1.3 mmol). The mixture was stirred for 12 h at RT, concentrated in vacuo, and partitioned between EtOAc and sat. NH4Cl. The aqueous phase was extracted with EtOAc (1×). The combined organic extracts were washed with sat. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography to provide (3-{2-[(1S,2S)-1-{[benzyloxycarbonyl-(2,4-dimethyl-benzyl)-amino]-methyl}-2-hydroxy-pentylcarbamoyl]-acetylamino}-5-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (577 mg, 75% yield). MS found: (M+Na)+=751.4.

1. concentrationconcentrated in vacuo
2. dissolutionThe residue was dissolved in benzene
3. concentrationconcentrated in vacuo
4. dissolutionThe resultant amine was dissolved in 15 mL of 2:1 CH2Cl2/DMF
5. stirringThe mixture was stirred for 12 h at RT
6. concentrationconcentrated in vacuo
7. custompartitioned between EtOAc and sat. NH4Cl
8. extractionThe aqueous phase was extracted with EtOAc (1×)
9. washThe combined organic extracts were washed with sat. NaHCO3 and brine
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe residue was purified by flash chromatography