Toluene → 4-{2-Amino-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}-2-fluoro-6-(methyloxy)benzonitrile
Reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[C:14](F)[C:11]([C:12]#[N:13])=[C:10]([F:17])[CH:9]=2)[CH:5]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][C@H:19]2[CH:24]([CH3:26])[CH3:25])[N:3]=1.C1(C)C=CC=CC=1.[CH3:34][O-:35].[Na+]>CN(C=O)C>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[C:14]([O:35][CH3:34])[C:11]([C:12]#[N:13])=[C:10]([F:17])[CH:9]=2)[CH:5]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][C@H:19]2[CH:24]([CH3:25])[CH3:26])[N:3]=1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
4-{2-Amino-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}-2,6-difluorobenzonitrile (380 mg, 1.06 mmol) was azeotroped with toluene (2×12 mL). The residue was dissolved in 5 mL of DMF as a clear yellow solution, to which was added NaOMe (2.30 mL of a stock solution with concentration of 0.52 mmol/mL, 1.19 mmol, 1.12 equiv) at room temperature in one portion. The resulting mixture was stirred at room temperature for 18 hours. LCMS showed conversion complete. The mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography using gradient elution of 1% EtOAc in CHCl3 to 100% EtOAc, providing the title compound (276 mg) as a light yellow oily residue. LC-MS (ES) m/z=372 [M+H]+.
Workup
- concentrationThe mixture was concentrated in vacuo
- customThe residue was purified by silica gel column chromatography
- washelution of 1% EtOAc in CHCl3 to 100% EtOAc
Sources & evidence
- ORD record
- ord-56cd6236c51d416aa69104dcd13a919f
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08697685B2
Reaction notes
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