Nitrogen → 6-{4-[2-(2,6-dichloro-phenyl)-4-isopropyl-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-2-methyl-benzofuran-3-carboxylic acid methyl ester

HRID 2261866Notes

Reaction equation

HRID 2261866 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:9]2[CH:10]=[CH:11][C:12](B3OC(C)(C)C(C)(C)O3)=[CH:13][C:8]=2[O:7][C:6]=1[CH3:23])=[O:4].Br[C:25]1[CH:48]=[CH:47][C:28]([O:29][CH2:30][C:31]2[N:35]([C:36]3[C:41]([Cl:42])=[CH:40][CH:39]=[CH:38][C:37]=3[Cl:43])[N:34]=[CH:33][C:32]=2[CH:44]([CH3:46])[CH3:45])=[CH:27][C:26]=1[CH3:49].N#N.C1(P(C2CCCCC2)C2(OC)CC=CC(OC)=C2C2C=CC=CC=2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:2][C:3]([C:5]1[C:9]2[CH:10]=[CH:11][C:12]([C:25]3[CH:48]=[CH:47][C:28]([O:29][CH2:30][C:31]4[N:35]([C:36]5[C:41]([Cl:42])=[CH:40][CH:39]=[CH:38][C:37]=5[Cl:43])[N:34]=[CH:33][C:32]=4[CH:44]([CH3:45])[CH3:46])=[CH:27][C:26]=3[CH3:49])=[CH:13][C:8]=2[O:7][C:6]=1[CH3:23])=[O:4]

Participants

9

Reactant 5

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 574433422-Methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzofuran-3-carboxylic acid methyl esterHCID 665453372-Dicyclohexylphosphino-2,6-dimethoxybiphenylHCID 675277775-(4-Bromo-3-methyl-phenoxymethyl)-1-(2,6-dichloro-phenyl)-4-isopropyl-1H-pyrazole

Product 1

HCID 675275966-{4-[2-(2,6-dichloro-phenyl)-4-isopropyl-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-2-methyl-benzofuran-3-carboxylic acid methyl esterYield 31%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 2-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzofuran-3-carboxylic acid methyl ester (162 mg, 0.512 mmol) and 5-(4-bromo-3-methyl-phenoxymethyl)-1-(2,6-dichloro-phenyl)-4-isopropyl-1H-pyrazole (256 mg, 0.563 mmol) in toluene (5 mL) is evacuated and refilled with N2 three times. Pd(OAc)2 (11.5 mg, 0.051 mmol), 2-dicyclohexylphosphino-2,6-dimethoxy-1,1′-biphenyl (42 mg, 0.102 mmol), and potassium phosphate (tribasic, N-hydrate, 218 mg, 1.02 mmol) in 0.5 mL of water are added. The resulting mixture is evacuated and refilled with N2 three times. The mixture is stirred at 110° C. for 16 hours and cooled to room temperature. The mixture is filtered through a pad of celite, and the filtrate is concentrated. The residue is purified by silica gel chromatography with 25% EtOAc/Hexanes to provide the product 6-{4-[2-(2,6-dichloro-phenyl)-4-isopropyl-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-2-methyl-benzofuran-3-carboxylic acid methyl ester (89 mg, 31%). ES/MS m/e 564.8 (M+1).

Workup

  1. customThe resulting mixture is evacuated
  2. additionrefilled with N2 three times
  3. temperaturecooled to room temperature
  4. filtrationThe mixture is filtered through a pad of celite
  5. concentrationthe filtrate is concentrated
  6. customThe residue is purified by silica gel chromatography with 25% EtOAc/Hexanes

Sources & evidence

ORD record
ord-a1fcf3fc86814a4384c0a43d4bae2dac
Source dataset
uspto-grants-2010_12
Patent number
US07846960B2

Reaction notes

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