1,2-Dimethoxyethane → 5-(2-chloro-phenyl)-1-[3'-(methylsulfanyl)-biphenyl-4-yl]-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazole

HRID 2208098Notes

Reaction equation

HRID 2208098 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[CH2:11][C:10]([C:20]([C:26]([F:29])([F:28])[F:27])([C:22]([F:25])([F:24])[F:23])[OH:21])=[N:9]2)=[CH:4][CH:3]=1.[CH3:30][S:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C.C(O)C>[Cl:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[CH:12]1[N:8]([C:5]2[CH:6]=[CH:7][C:2]([C:36]3[CH:35]=[CH:34][CH:33]=[C:32]([S:31][CH3:30])[CH:37]=3)=[CH:3][CH:4]=2)[N:9]=[C:10]([C:20]([C:22]([F:24])([F:23])[F:25])([C:26]([F:28])([F:29])[F:27])[OH:21])[CH2:11]1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27343833-(Methylthio)benzeneboronic acidHCID 1184316661-(4-Bromo-phenyl)-5-(2-chloro-phenyl)-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazole

Product 1

HCID 1184319845-(2-chloro-phenyl)-1-[3'-(methylsulfanyl)-biphenyl-4-yl]-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazoleYield 6.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

1-(4-Bromo-phenyl)-5-(2-chloro-phenyl)-3-[di-(trifluoromethyl)-hydroxy-methyl]-4,5-dihydro-1H-pyrazole (50.0 mg, 0.10 mmol) prepared in Step 5 of Preparation 24, 3-methylthiophenylboronic acid (25.1 mg, 0.15 mmol), Pd(PPh3)4 (11.5 mg, 0.01 mmol), and a 2N sodium carbonate solution (0.5 mL) were added to a mixed solvent of 1,2-dimethoxyethane (2.0 mL) and ethanol (0.5 mL). The reaction mixture was stirred at 90° C. for 2 hours and then ethyl acetate was added thereto. The reaction mixture was washed with distilled water and brine, dried on anhydrous magnesium sulfate, and then concentrated under reduced pressure to give a yellow liquid residue. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/10) to give 3.7 mg of the titled compound as a yellow liquid.

Workup

  1. washThe reaction mixture was washed with distilled water and brine
  2. dry with materialdried on anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto give a yellow liquid residue
  5. customThe resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/10)

Sources & evidence

ORD record
ord-a9e439492ffb4dec85c713e9abf1ad30
Source dataset
uspto-grants-2016_06
Patent number
US09376420B2

Reaction notes

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