Potassium Carbonate → Methyl [3,5-bis(trifluoromethyl)benzyl][(5'-isopropyl-2'-methoxy-4-pyridin-3-ylbiphenyl-2-yl)methyl]carbamate

HRID 17044

Reaction equation

HRID 17044 reaction equation
[F:1][C:2]([F:39])([F:38])[C:3]1[CH:4]=[C:5]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=1)[CH2:6][N:7]([CH2:12][C:13]1[CH:18]=[C:17](I)[CH:16]=[CH:15][C:14]=1[C:20]1[CH:25]=[C:24]([CH:26]([CH3:28])[CH3:27])[CH:23]=[CH:22][C:21]=1[O:29][CH3:30])[C:8](=[O:11])[O:9][CH3:10].C(=O)([O-])[O-].[K+].[K+].[N:46]1[CH:51]=[CH:50][CH:49]=[C:48](B(O)O)[CH:47]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC(C)=O.O>[F:1][C:2]([F:39])([F:38])[C:3]1[CH:4]=[C:5]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=1)[CH2:6][N:7]([CH2:12][C:13]1[CH:18]=[C:17]([C:48]2[CH:47]=[N:46][CH:51]=[CH:50][CH:49]=2)[CH:16]=[CH:15][C:14]=1[C:20]1[CH:25]=[C:24]([CH:26]([CH3:28])[CH3:27])[CH:23]=[CH:22][C:21]=1[O:29][CH3:30])[C:8](=[O:11])[O:9][CH3:10]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 11527580Methyl [3,5-bis(trifluoromethyl)benzyl][(4-iodo-5'-isopropyl-2'-methoxybiphenyl-2-yl)methyl]carbamate

Product 1

HCID 11527369Methyl [3,5-bis(trifluoromethyl)benzyl][(5'-isopropyl-2'-methoxy-4-pyridin-3-ylbiphenyl-2-yl)methyl]carbamate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 18366337Propan-2-one--water (1/1)Solvent

Procedure

A mixture of methyl [3,5-bis(trifluoromethyl)benzyl][(4-iodo-5′-isopropyl-2′-methoxybiphenyl-2-yl)methyl]carbamate from Example 10 (0.03 g, 0.045 mmol), potassium carbonate (0.012 g, 0.09 mmol), 3-pyridyl boronic acid (0.0066 g, 0.054 mmol) and a catalytic amount of palladium acetate (1 mg) in 4:1 acetone/water (2 ml) was heated to and maintained at reflux for 5 h. Acetone was removed and the organic was extracted with methylene chloride (3×10 ml). The combined organic layers were washed with brine and dried over sodium sulfate. The title compound was obtained after preparative thin layer chromatography using 3:7 EtOAc/hexane as the eluant. 1H NMR (CDCl3, 500 MHz) δ 8.90 (m, 1H), 8.65 (m, 1H), 7.90 (m, 1H), 7.72 (s, 1H), 7.70 (m, 1H), 7.60 (dd, J=8.0, 2.5 Hz, 1H), 7.48 (m, 2H), 7.39 (d, J=8.0 Hz, 1H), 7.35 (s, 1H), 7.25 (m, 1H), 7.00 (s, 1H), 6.93 (d, J=8.0 Hz, 1H), 4.20-4.62 (m, 4H), 3.77 (s, 3H), 3.72 (s, 3H), 2.90 (m, 1H), 1.22 (s, 6H). LC-MS (M+1) 617.0 (3.76 min).

Workup

  1. temperaturemaintained
  2. temperatureat reflux for 5 h
  3. customAcetone was removed
  4. extractionthe organic was extracted with methylene chloride (3×10 ml)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-d5a60933e108403abf9e0385a3e8c05f
Source dataset
uspto-grants-2010_06
Patent number
US07737295B2

Linked notes

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