Pyridine → 4-((5-ethoxy-2-fluoro-3-isopropoxyphenyl)(1-phenyl-1H-pyrazol-3-yl)methylamino)benzonitrile
Reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([O:26][CH:27]([CH3:29])[CH3:28])[C:7]([F:25])=[C:8]([N:10]([CH2:19][C:20]2[CH:24]=[CH:23][NH:22][N:21]=2)[C:11]2[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][CH:12]=2)[CH:9]=1)[CH3:2].N1C=CC=CC=1.[C:36]1(B(O)O)[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.B(O)O>C(Cl)Cl.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Cu+2]>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([O:26][CH:27]([CH3:28])[CH3:29])[C:7]([F:25])=[C:8]([N:10]([CH2:19][C:20]2[CH:24]=[CH:23][N:22]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[N:21]=2)[C:11]2[CH:12]=[CH:13][C:14]([C:15]#[N:16])=[CH:17][CH:18]=2)[CH:9]=1)[CH3:2]Participants
8
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Procedure
To a mixture of Intermediate 183.1 (39.5 mg, 0.100 mmol) and 3A molecular sieves (30 mg) in 1 mL CH2Cl2 at rt, was added TEA (0.028 mL, 0.20 mmol), pyridine (16 mg, 0.20 mmol) and phenylboronic acid (24.4 mg, 0.20 mmol). The mixture was stirred until the boronic acid dissolved, then Cu(OAc)2 (27.3 mg, 0.150 mmol) was added. The mixture was stirred for 5.5 h, then was diluted with EtOAc. The organic phase was washed with 0.5N HCl, H2O, sat. NaHCO3 and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 50% EtOAc/hexanes gradient) to afford 33.4 mg of Intermediate 183.2 as a pale yellow solid.
Workup
- dissolutiondissolved
- washThe organic phase was washed with 0.5N HCl, H2O, sat. NaHCO3 and brine
- dry with materialdried (Na2SO4)
- concentrationconcentrated
- customThe crude product was purified by flash chromatography (0 to 50% EtOAc/hexanes gradient)
Sources & evidence
- ORD record
- ord-298f58f917e640c2982473f620523590
- Source dataset
- uspto-grants-2009_08
- Patent number
- US07576098B2
Reaction notes
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