Water → 2,6-Dichloro-N-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]pyrimidin-4-amine
Reaction equation
Cl.[F:2][C:3]1[CH:4]=[CH:5][C:6]([C@@H:9]([NH2:11])[CH3:10])=[N:7][CH:8]=1.CCN(C(C)C)C(C)C.[Cl:21][C:22]1[N:27]=[C:26](Cl)[CH:25]=[C:24]([Cl:29])[N:23]=1.O>C(O)C>[Cl:21][C:22]1[N:27]=[C:26]([NH:11][C@H:9]([C:6]2[CH:5]=[CH:4][C:3]([F:2])=[CH:8][N:7]=2)[CH3:10])[CH:25]=[C:24]([Cl:29])[N:23]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
(S)-1-(5-Fluoropyridin-2-yl)ethanamine hydrochloride (prepared as described in WO2006/123113, 1.05 g, 4.91 mmol) and N,N′-diisopropylethylamine (2.80 mL, 16.36 mmol) were added to a solution of 2,4,6-trichloropyrimidine (0.75 g, 4.09 mmol) in ethanol (15 mL) and the resulting mixture was stirred and heated to 80° C. in a sealed tube for 1 hour. After cooling to ambient temperature, water was added and the resulting mixture was extracted with ethyl acetate (×3). The combined organic layers were washed with water and brine, dried (MgSO4), filtered and the solvent evaporated under reduced pressure. The residue was purified by flash chromatography (hexanes to 1:1 hexanes/ethyl acetate) to give the title compound (0.66 g, 57%) as a white solid.
Workup
- temperatureAfter cooling to ambient temperature
- extractionthe resulting mixture was extracted with ethyl acetate (×3)
- washThe combined organic layers were washed with water and brine
- dry with materialdried (MgSO4)
- filtrationfiltered
- customthe solvent evaporated under reduced pressure
- customThe residue was purified by flash chromatography (hexanes to 1:1 hexanes/ethyl acetate)
Sources & evidence
- ORD record
- ord-9383b83231e4474382558d19e5e8a8ab
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09034311B2
Reaction notes
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