反应详情

A mixture of tert-butyl methyl((2S)-1-oxo-1-(4-oxo-2′,3′,4,5,5′,6′-hexahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4′-pyran]-3-ylamino)propan-2-yl)carbamate (118 mg, 272 μmol), (2-(difluoromethoxy)naphthalen-1-yl)methyl methanesulfonate (98.7 mg, 327 μmol) and Cs2CO3 (115 mg, 354 μmol) in DMF (681 μL) was stirred at RT for 20 h. The mixture was diluted with EtOAc, washed with H2O and brine, then dried over Na2SO4, and filtered. The filtrate was concentrated to give a residue that was purified by silica gel chromatography. The resulting material was purified by SFC to provide tert-butyl (S)-1-((S)-5-((2-(difluoromethoxy)naphthalen-1-yl)methyl)-4-oxo-2′,3′,4,5,5′,6′-hexahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4′-pyran]-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (52.6 mg, 30%) as a white foam (MS m/z 662 (MNa)′) and tert-butyl (S)-1-((R)-5-((2-(difluoromethoxy)naphthalen-1-yl)methyl)-4-oxo-2′,3′,4,5,5′,6′-hexahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4′-pyran]-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (72.8 mg, 42%) as a white foam (MS m/z 662 (MNa)+).

1. washwashed with H2O and brine
2. dry with materialdried over Na2SO4
3. filtrationfiltered
4. concentrationThe filtrate was concentrated
5. customto give a residue that
6. customwas purified by silica gel chromatography
7. customThe resulting material was purified by SFC