反应详情

A solution of 0.18 g (0.37 mmol) of (13S,16R)-16-amino-13-isopropyl-2,11-dioxa-14-azabicyclo[16.2.2]docosa-1(21),18(22),19-trien-15-one in 3.8 ml of DMF was added to 60 mg (0.37 mmol) of 1,1′-carbonyldiimidazole and, after addition of 0.2 ml (0.15 g, 1.47 mmol) of triethylamine, stirred under argon. After 10 min, 124 mg (0.37 mmol) of tert-butyl(S)-2-amino-6-tert-butoxycarbonylaminohexanoate hydrochloride were added, and the mixture was stirred for 3 h. It was concentrated and partitioned between water and ethyl acetate, and the organic phase was dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative HPLC. The required fractions were combined and concentrated. The residue was taken up in 20 ml of dichloromethane/TFA (1:1, v/v) and left to stand for 2 h. The mixture was concentrated, dissolved in 1N hydrochloric acid with a little acetonitrile and freeze dried. An amorphous solid (0.12 g) was obtained as hydrochloride.

1. stirringthe mixture was stirred for 3 h
2. concentrationIt was concentrated
3. custompartitioned between water and ethyl acetate
4. dry with materialthe organic phase was dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by preparative HPLC
8. concentrationconcentrated
9. waitv/v) and left
10. waitto stand for 2 h
11. concentrationThe mixture was concentrated
12. dissolutiondissolved in 1N hydrochloric acid with a little acetonitrile and freeze
13. customdried