Water → (S)-S-2-(2-chloro-5-fluoropyrimidin-4-ylamino)-3,3-dimethylbutyl ethanethioate
Reaction equation
[C:1]([O-:4])(=[S:3])[CH3:2].[K+].CS(O[CH2:11][C@@H:12]([NH:17][C:18]1[C:23]([F:24])=[CH:22][N:21]=[C:20]([Cl:25])[N:19]=1)[C:13]([CH3:16])([CH3:15])[CH3:14])(=O)=O.O>CN(C=O)C>[C:1](=[O:4])([S:3][CH2:11][C@@H:12]([NH:17][C:18]1[C:23]([F:24])=[CH:22][N:21]=[C:20]([Cl:25])[N:19]=1)[C:13]([CH3:16])([CH3:14])[CH3:15])[CH3:2]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 78 °C
Procedure
Potassium thioacetate (1.30 g, 11.51 mmol) was added to a stirring solution of (S)-2-(2-chloro-5-fluoropyrimidin-4-ylamino)-3,3-dimethylbutyl methanesulfonate, 75a, (2.50 g, 7.67 mmol) in dry DMF (50 mL). The resulting brown solution was heated with stirring at 78° C. for 1 hour. The brown suspension was poured into water and extracted with EtOAc (3×100 mL). The combined organic phases were dried (MgSO4), filtered and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (0-30% EtOAc/Hexanes gradient) to afford 2.1 g of compound 76a as a pale brown solid: 1H NMR (400 MHz, CDCl3) δ 7.81 (s, 1H), 5.12 (m, 1H), 4.21 (t, J=9.1 Hz, 1H), 3.15-2.90 (m, 2H), 2.23 (s, 3H), 0.95 (m, 9H); LC/MS (10-90% ACN/water 5 min with 0.9% FA) m/z 306.02 (M+H) RT=3.32 min.
Workup
- temperatureThe resulting brown solution was heated
- extractionextracted with EtOAc (3×100 mL)
- dry with materialThe combined organic phases were dried (MgSO4)
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe crude residue was purified by silica gel chromatography (0-30% EtOAc/Hexanes gradient)
Sources & evidence
- ORD record
- ord-a41cb09745ef4fb08ea3bda911a4e2e4
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09394302B2
Reaction notes
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