Ammonia → (R)-5-(2-fluoro-phenyl)-2,2,5-trimethyl-1,1-dioxo-1,2,5,6-tetrahydro-1lambda6-[1,4]thiazin-3-ylamine
Reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:20])=[C:6]([C@:8]2([CH3:19])[CH2:13][S:12](=[O:15])(=[O:14])[C:11]([CH3:17])([CH3:16])[C:10]([NH2:18])=[N:9]2)[CH:7]=1.N>CO.[Pd]>[F:20][C:5]1[CH:4]=[CH:3][CH:2]=[CH:7][C:6]=1[C@:8]1([CH3:19])[CH2:13][S:12](=[O:14])(=[O:15])[C:11]([CH3:16])([CH3:17])[C:10]([NH2:18])=[N:9]1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 23 °C
Procedure
To a solution of (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, Eq: 1.00) in methanol (80 ml) and ammonia (7 M in MeOH) (1.18 ml, 8.26 mmol, Eq: 3.0) was added at 23° C. under inert atmosphere Pd/C 10% (293 mg, 275 μmol, Eq: 0.1) and the suspension was set under hydrogen (balloon) and stirred at 23° C. for 2 hours. The catalyst was filtered off, washed three times with methanol and evaporated. The residue was extracted with dichloromethane/sat. NaHCO3-sol. and the organic layer was dried over Na2SO4, filtered and evaporated to give the pure (R)-5-(2-fluoro-phenyl)-2,2,5-trimethyl-1,1-dioxo-1,2,5,6-tetrahydro-1λ6-[1,4]thiazin-3-ylamine (760 mg, 2.67 mmol, 97.1% yield) as a white solid. MS (ISP): m/z=285.4 [M+H]+.
Workup
- filtrationThe catalyst was filtered off
- washwashed three times with methanol
- customevaporated
- extractionThe residue was extracted with dichloromethane/
- dry with materialand the organic layer was dried over Na2SO4
- filtrationfiltered
- customevaporated
Sources & evidence
- ORD record
- ord-2dfce68a11974bd28a933f505d998db9
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09273042B2
Reaction notes
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