Ammonia → (R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-1,1-dioxo-1,2,5,6-tetrahydro-1lambda6-[1,4]thiazin-3-ylamine

HRID 920168Notes

Reaction equation

HRID 920168 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]=1

Participants

3

Reactant 2

HCID 222AmmoniaHCID 90067090(R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-1,1-dioxo-1lambda6-thio morpholin-3-thione

Product 1

HCID 90067098(R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-1,1-dioxo-1,2,5,6-tetrahydro-1lambda6-[1,4]thiazin-3-ylamineYield 69.3%

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]+.

Workup

  1. customThe yellow solution was evaporated
  2. customchromatographed on 20 g silica gel with 0-80% ethyl acetate in heptane

Sources & evidence

ORD record
ord-0303220d010244ef9fd8338beba10e05
Source dataset
uspto-grants-2016_03
Patent number
US09273042B2

Reaction notes

Loading…