Tricyclohexylphosphine → HCID 44177595, compound

HRID 1673038Notes

Reaction equation

HRID 1673038 reaction equation
Br[C:2]1[N:3]=[C:4]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:29]([F:32])([F:31])[F:30])[N:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([S:19]([CH3:22])(=[O:21])=[O:20])[CH:14]=3)=[CH:9][CH:8]=2)[CH:6]=1.[CH:33]1(B(O)[OH:37])[CH2:35][CH2:34]1.P(C1CCCCC1)(C1CCCCC1)C1CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[OH2:66]>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:24]([OH:37])([C:29]([F:32])([F:31])[F:30])=[O:66].[CH:33]1([C:2]2[N:3]=[C:4]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[C:29]([F:32])([F:31])[F:30])[N:5]([C:7]3[CH:12]=[CH:11][C:10]([C:13]4[CH:18]=[CH:17][CH:16]=[C:15]([S:19]([CH3:22])(=[O:21])=[O:20])[CH:14]=4)=[CH:9][CH:8]=3)[CH:6]=2)[CH2:35][CH2:34]1

Participants

9

Reactant 4

HCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 59240043HCID 59240043, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 44177595HCID 44177595, compoundYield 54%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of compound 4-bromo-1-(3′-(methylsulfonyl)biphenyl-4-yl)-2-(2-(trifluoromethyl)phenyl)-1H-imidazole (224 mg, 0.430 mmol), cyclopropyl boronic acid (55 mg, 0.640 mmol), P(Cy)3 (23 mg, 0.082 mmol) and K3PO4.H2O (345 mg, 1.50 mmol) in 2.5 mL toluene and 0.15 mL H2O was added Pd(OAc)2 (10 mg, 0.044 mmol) in a 5 mL microwave tube. The tube was sealed and purged with an argon balloon for five minutes. The reaction was stirred for 24 h at 100° C. and cooled to room temperature. The reaction was diluted with ethyl acetate, and washed with saturated NH4Cl, brine, dried with MgSO4 and the solvent removed in vacuo. The residue was purified by column chromatography using hexanes:ethyl acetate as eluents and further purified by preparatory HPLC using water:TFA:acetonitrile as eluents to afford 4-cyclopropyl-1-(3′-(methylsulfonyl)biphenyl-4-yl)-2-(2-(trifluoromethyl)phenyl)-1H-imidazole (56 mgs, 27%) as a white solid. 1H-NMR (DMSO, 400 MHz) δ 8.13-8.12 (m, 1H), 8.03-8.00 (m, 1H), 7.91-7.88 (m, 1H), 7.83-7.80 (m, 1H), 7.77 (d, J=8.58 Hz, 2H), 7.74-7.69 (m, 1H), 7.64-7.62 (m, 2H), 7.46-7.44 (m, 1H), 7.41 (s, 1H), 7.25 (d, J=8.58 Hz, 2H), 3.28 (s, 3H), 1.93-1.87 (m, 1H), 0.86-0.82 (m, 2H), 0.76-0.72 (m, 2H); MS (ES): 483.0 [M+H]+.

Workup

  1. customThe tube was sealed
  2. custompurged with an argon balloon for five minutes
  3. temperaturecooled to room temperature
  4. additionThe reaction was diluted with ethyl acetate
  5. washwashed with saturated NH4Cl, brine
  6. dry with materialdried with MgSO4
  7. customthe solvent removed in vacuo
  8. customThe residue was purified by column chromatography
  9. customethyl acetate as eluents and further purified by preparatory HPLC

Sources & evidence

ORD record
ord-76d9d7a331734834a00d62991f3f5918
Source dataset
uspto-grants-2011_08
Patent number
US07998995B2

Reaction notes

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