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

HRID 920170Notes

Reaction equation

HRID 920170 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:20])=[C:6]([C@@:8]2([CH3:19])[NH:13][C:12](=S)[C:11]([CH3:16])([CH3:15])[S:10](=[O:18])(=[O:17])[CH2:9]2)[CH:7]=1.[NH3:21]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:20])=[C:6]([C@:8]2([CH3:19])[CH2:9][S:10](=[O:18])(=[O:17])[C:11]([CH3:16])([CH3:15])[C:12]([NH2:21])=[N:13]2)[CH:7]=1

Participants

3

Reactant 2

HCID 222AmmoniaHCID 90067099(R)-5-(5-bromo-2-fluoro-phenyl)-2,2,5-trimethyl-1,1-dioxo-1lambda6-thiomorpholin-3-thione

Product 1

HCID 86715707(R)-5-(5-bromo-2-fluoro-phenyl)-2,2,5-trimethyl-1,1-dioxo-1,2,5,6-tetrahydro-1lambda6-[1,4]thiazin-3-ylamineYield 81.8%

Conditions

Temperature
60 °C

Procedure

A mixture of (R)-5-(5-bromo-2-fluoro-phenyl)-2,2,5-trimethyl-1,1-dioxo-1λ6-thiomorpholin-3-thione (1.28 g, 3.37 mmol, Eq: 1.00) and ammonia (7 N in MeOH) (38.5 ml, 269 mmol, Eq: 80) was stirred in a sealed tube for 20 hours at 60° C. Extracted with ethyl acetate/sat. NaHCO3-sol., dried the organic layer over Na2SO4, filtered and evaporated. The residue was chromatographed with ethyl acetate to give (R)-5-(5-bromo-2-fluoro-phenyl)-2,2,5-trimethyl-1,1-dioxo-1,2,5,6-tetrahydro-1λ6-[1,4]thiazin-3-ylamine (1 g, 2.75 mmol, 81.8% yield) as a white solid. MS (ISP): m/z=363.3 [M+H]+ and 365.3 [M+2+H]+.

Workup

  1. extractionExtracted with ethyl acetate/
  2. dry with material, dried the organic layer over Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was chromatographed with ethyl acetate

Sources & evidence

ORD record
ord-4cfc909385a54f23b44ef5029cc1662a
Source dataset
uspto-grants-2016_03
Patent number
US09273042B2

Reaction notes

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