Imidazole → 5-(1H-Imidazol-2-yl)-4'-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide
Reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:30][O:31][CH2:32][CH:33]([NH:35][C:36]([C:38]1[CH:39]=[C:40]([C:45]2[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][CH:46]=2)[CH:41]=[C:42](I)[CH:43]=1)=[O:37])[CH3:34]>O1CCOCC1.O.[Cu]I.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:30][O:31][CH2:32][CH:33]([NH:35][C:36]([C:38]1[CH:39]=[C:40]([C:45]2[CH:46]=[CH:47][C:48]([CH3:51])=[CH:49][CH:50]=2)[CH:41]=[C:42]([C:2]2[NH:1][CH:5]=[CH:4][N:3]=2)[CH:43]=1)=[O:37])[CH3:34]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 150 °C
Procedure
Imidazole (200 mg, 2.9 mmol) and MgO (60 mg, 2.9 mmol) were suspended in 0.5 ml dry dioxane and 2.5 ml dry DMF in a reaction bottle and stirred at room temperature for 5 minutes to form a homogeneous suspension. CuI (300 mg, 1.5 mmol), Pd(OAc)2 (18 mg, 0.0734 mmol), PPh3 (60 mg, 0.22 mmol) and 5-iodo-4′-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide (300 mg, 0.7335 mmol) were added to the above solution and reaction mixture were heated to 150° C. under microwave irradiation for 45 minutes. The reaction mixture was cooled, diluted with water, extracted with ethyl acetate, washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by preparative HPLC to give 165 mg of 5-(1H-Imidazol-2-yl)-4′-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide (65%), MS (M+H)=350.
Workup
- customto form a homogeneous suspension
- temperatureThe reaction mixture was cooled
- extractionextracted with ethyl acetate
- washwashed with brine
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue was purified by preparative HPLC
Sources & evidence
- ORD record
- ord-347b4d20bb08452b9b1aa96c4d1358ac
- Source dataset
- uspto-grants-2010_12
- Patent number
- US07858654B2
Reaction notes
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