Nitrogen → 3-(3-fluoro-4-(4-hydroxypiperidin-1-yl)phenyl)-2,6-dimethylpyrimidin-4(3H)-one
Reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)=[C:4]([F:15])[CH:3]=1.C[Al](C)C.N#N.[NH:22](/[C:26](/[CH3:32])=[CH:27]\[C:28](OC)=[O:29])[C:23]([CH3:25])=O>C(Cl)Cl>[F:15][C:4]1[CH:3]=[C:2]([N:1]2[C:28](=[O:29])[CH:27]=[C:26]([CH3:32])[N:22]=[C:23]2[CH3:25])[CH:7]=[CH:6][C:5]=1[N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 1-(4-amino-2-fluorophenyl)piperidin-4-ol (1.68 g, 8.00 mmol) in CH2Cl2 (20 mL) was added trimethylaluminium (32 mL, 64 mmol, 2 M in heptane) carefully under N2. The mixture was stirred at rt for 30 min, followed by the addition of a solution of methyl 3-acetaminocrotonate (1.40 g, 8.90 mol) in CH2Cl2 (5 mL). The reaction mixture was stirred at rt for another 5 h, then quenched with saturated NH4Cl aqueous solution (100 mL). The organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by recrystallized from EtOAc to give the title compound as a yellow solid (1.25 g, 50%). The compound was characterized by the following spectroscopic data:
Workup
- stirringThe reaction mixture was stirred at rt for another 5 h
- customquenched with saturated NH4Cl aqueous solution (100 mL)
- dry with materialThe organic phase was dried over anhydrous Na2SO4
- concentrationconcentrated in vacuo
- customThe residue was purified
- customby recrystallized from EtOAc
Sources & evidence
- ORD record
- ord-cb971c3c31fc4a6289e7dd1babd85f44
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09434695B2
Reaction notes
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