Pyridine → {4-[4-(3-Methoxy-5-phenylamino-pyridin-2-yl)-phenyl]-cyclohexyl}-acetic acid methyl ester

HRID 76059Notes

Reaction equation

HRID 76059 reaction equation
[CH3:1][O:2][C:3](=[O:26])[CH2:4][CH:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[C:22]([O:23][CH3:24])=[CH:21][C:20]([NH2:25])=[CH:19][N:18]=3)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.[C:27]1(B(O)O)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.N1C=CC=CC=1>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCl>[CH3:1][O:2][C:3](=[O:26])[CH2:4][CH:5]1[CH2:6][CH2:7][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[C:22]([O:23][CH3:24])=[CH:21][C:20]([NH:25][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[CH:19][N:18]=3)=[CH:13][CH:12]=2)[CH2:9][CH2:10]1

Participants

6

Reactant 3

HCID 1049PyridineHCID 66827Phenylboronic AcidHCID 66615823{4-[4-(5-Amino-3-methoxy-pyridin-2-yl)-phenyl]-cyclohexyl}-acetic acid methyl ester

Product 1

HCID 66615934{4-[4-(3-Methoxy-5-phenylamino-pyridin-2-yl)-phenyl]-cyclohexyl}-acetic acid methyl ester

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of {4-[4-(5-Amino-3-methoxy-pyridin-2-yl)-phenyl]-cyclohexyl}-acetic acid methyl ester (0.12 g, 0.3 mmol, 1.0 equiv) and phenyl boronic acid (0.082 g, 0.67 mmol, 2.0 equiv) in 5 Ml dichloromethane was added pyridine (0.054 Ml, 0.67 mmol, 2.0 equiv), copper (II) acetate (0.092 g, 0.50 mmol, 1.5 equiv), and 4 Å molecular sieves. The heterogeneous reaction mixture was allowed to stir open to atmosphere for 18 h. Removal of solvent and purification by silica gel chromatography (40% EtOAc in hexanes) afforded the title compound: 1H NMR (400 MHz, DMSO-d6) δ ppm 1.14-1.31 (m, 2H) 1.50 (br. S., 1H) 1.55 (dd, J=12.51, 2.40 Hz, 2H) 1.87 (d, J=12.38 Hz, 5H) 2.31 (d, J=6.57 Hz, 2H) 3.66 (s, 3H) 3.86 (s, 3H) 6.96 (t, J=7.33 Hz, 1H) 7.20-7.38 (m, 7H) 7.82 (d, J=8.34 Hz, 2H) 8.11 (d, J=2.02 Hz, 1H) 8.53 (s, 1H); (M+H)+431.2.

Workup

  1. customRemoval of solvent and purification by silica gel chromatography (40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-ad8909eed54940989a157228eb2f075f
Source dataset
uspto-grants-2014_09
Patent number
US08835451B2

Reaction notes

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