Toluene → 3-(1-Phenylsulfonyl-4-[2-(3-fluoro-phenyl)-vinyl]-1h-pyrazol-3-yl)-pyridine

HRID 660169Notes

Reaction equation

HRID 660169 reaction equation
C1(C)C=CC=CC=1.[C:8]1([S:14]([N:17]2[CH:21]=[C:20](Br)[C:19]([C:23]3[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=3)=[N:18]2)(=[O:16])=[O:15])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[F:29][C:30]1[CH:31]=[C:32](/[CH:36]=[CH:37]/B(O)O)[CH:33]=[CH:34][CH:35]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>[C:8]1([S:14]([N:17]2[CH:21]=[C:20]([CH:37]=[CH:36][C:32]3[CH:33]=[CH:34][CH:35]=[C:30]([F:29])[CH:31]=3)[C:19]([C:23]3[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=3)=[N:18]2)(=[O:16])=[O:15])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 16217749B-[(1E)-2-(3-Fluorophenyl)ethenyl]boronic acidHCID 575480773-(1-Phenylsulfonyl-4-bromo-1H-pyrazol-3-yl)-pyridine

Product 1

HCID 672850093-(1-Phenylsulfonyl-4-[2-(3-fluoro-phenyl)-vinyl]-1h-pyrazol-3-yl)-pyridineYield 73%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To toluene (20 ml) containing 36A (0.48 g, 1.32 mmol) (see Scheme 7), was added 1.5 eq of (E)-2-(3-fluorphenyl)-vinyl boronic acid (0.33 g). The resulting mixture was stirred for 2 hours under N2. Successively were added 2 eq of K3PO4 (0.56 g), 4 mol % of Pd(OAc)2 (8.8 mg) and 8 mol % of S-Phos (32 mg). After the addition, the resulting solution was warmed at 90° C. for 18 hours under N2. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed three times with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to afford 3-(1-phenylsulfonyl-4-[2-(3-fluoro-phenyl)-vinyl]-1H-pyrazol-3-yl)-pyridine (46B) as an oil (0.39 g, 73%). 1H-NMR (400 MHz, CDCl3): δ 8.85 (d, J=2 Hz, 1H), 8.65 (dd, J=5 Hz, 2 Hz, 1H), 8.36 (s, 1H), 8.13-8.08 (m, 2H), 7.95 (dt, J=8 Hz, 2 Hz, 1H), 7.72-7.67 (m, 1H), 7.58 (bt, J=8 Hz, 2H), 7.41-7.37 (m, 1H), 7.33-7.27 (m, 1H), 7.16 (bd, J=7 Hz, 1H), 7.12-7.07 (m, 1H), 7.0-6.94 (m, 1H), 6.92 (d, J=16 Hz, 1H), 6.82 (d, J=16 Hz, 1H).

Workup

  1. additionAfter the addition
  2. temperatureAfter cooling to room temperature
  3. washwashed three times with a saturated NaHCO3 solution
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Sources & evidence

ORD record
ord-a8bc9dd85d0d4073a0eb392ed34bbbbe
Source dataset
uspto-grants-2011_12
Patent number
US08084473B2

Reaction notes

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