Methyl iodide → (S)-2-chloro-N-(3,3-dimethyl-1-(methylthio)butan-2-yl)-5-fluoropyrimidin-4-amine
Reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@@H:9]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:10][SH:11])[C:5]([F:16])=[CH:4][N:3]=1.[C:17]([O-])([O-])=O.[K+].[K+].IC>CC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@@H:9]([C:12]([CH3:13])([CH3:15])[CH3:14])[CH2:10][S:11][CH3:17])[C:5]([F:16])=[CH:4][N:3]=1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 70 °C
Procedure
To a suspension of (S)-2-(2-chloro-5-fluoropyrimidin-4-ylamino)-3,3-dimethylbutane-1-thiol, 77a, (0.85 g, 3.60 mmol) and K2CO3 (2.26 g, 16.35 mmol) in acetone was added iodomethane (0.82 mL, 13.08 mmol). The suspension was heated at 70° C. for 1.30 hours and then cooled to room temperature. The solid was filtered and the solution was concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (0-10% EtOAc/Hexanes gradient) to afford 310 mg of the desired product as a white 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 (60-90% ACN/water 5 min with 0.9% FA) m/z 278.29 (M+H) RT =1.35 minutes.
Workup
- temperaturecooled to room temperature
- filtrationThe solid was filtered
- concentrationthe solution was concentrated under reduced pressure
- customThe crude residue was purified by silica gel chromatography (0-10% EtOAc/Hexanes gradient)
Sources & evidence
- ORD record
- ord-bbdbdf82a7c4452491a2ed1cfca638d8
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09394302B2
Reaction notes
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