Sodium hydride → (2-Chloro-pyrimidin-4-yl)-[1-(3-ethoxy-4-methoxy-benzyl)-piperidin-4-yl]-amine
Reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:15]=[CH:16][C:17]=1[O:18][CH3:19])[CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]1)[CH3:2].[H-].[Na+].[Cl:22][C:23]1[N:28]=[C:27](Cl)[CH:26]=[CH:25][N:24]=1>CN(C=O)C>[Cl:22][C:23]1[N:28]=[C:27]([NH:14][CH:11]2[CH2:10][CH2:9][N:8]([CH2:7][C:6]3[CH:15]=[CH:16][C:17]([O:18][CH3:19])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=3)[CH2:13][CH2:12]2)[CH:26]=[CH:25][N:24]=1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 1-(3-ethoxy-4-methoxy-benzyl)-piperidin-4-ylamine (39.7 mg, 0.15 mmol, 1.2 equiv; intermediate A1) in dry DMF (1.5 mL) under Ar was added sodium hydride (6.6 mg, 0.15 mmol, 1.2 equiv; 55% free-flowing powder moistened with oil) and the reaction mixture stirred at rt. After 2 h, 2,4-dichloro-pyrimidine (18.6 mg, 0.125 mmol, 1.0 equiv; commercially available) was added and the mixture heated by microwave irradiation to 140° C. for 1 h. Removal of the solvent under reduced pressure and purification by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water provided 10.9 mg (23%) of the title compound. MS (ISP): 377.2 [M+H]+.
Workup
- additioncommercially available) was added
- temperaturethe mixture heated by microwave irradiation to 140° C. for 1 h
- customRemoval of the solvent
- customunder reduced pressure and purification by preparative HPLC on reversed phase
- washeluting with a gradient of acetonitrile/water
Sources & evidence
- ORD record
- ord-c677f6cc1c9242c5b0e77880529c21c1
- Source dataset
- uspto-grants-2011_06
- Patent number
- US07968568B2
Reaction notes
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