Ammonia → (R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-1,1-dioxo-1,2,5,6-tetrahydro-1lambda6-[1,4]thiazin-3-ylamine
Reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C@@:8]2([CH3:17])[NH:13][C:12](=S)[CH2:11][S:10](=[O:16])(=[O:15])[CH2:9]2)[CH:7]=1.[NH3:19]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C@:8]2([CH3:17])[CH2:9][S:10](=[O:16])(=[O:15])[CH2:11][C:12]([NH2:19])=[N:13]2)[CH:7]=1Participants
3
Conditions
- Temperature
- 60 °C
Procedure
A mixture of (R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-1,1-dioxo-1λ6-thiomorpholin-3-thione (2.7 g, 7.67 mmol, Eq: 1.00) in ammonia (7 M in MeOH) (47.2 g, 60 ml, 420 mmol, Eq: 54.8) was stirred at 60° C. in a sealed tube for 5 hours. The yellow solution was evaporated, then chromatographed on 20 g silica gel with 0-80% ethyl acetate in heptane to give the (R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-1,1-dioxo-1,2,5,6-tetrahydro-1λ6-[1,4]thiazin-3-ylamine (1.78 g, 5.31 mmol, 69.3% yield) as a white foam. MS (ISP): m/z=335.0 [M+H]+ and 337.0 [M+2+H]+.