Water → HCID 11359727, compound

HRID 746834Notes

Reaction equation

HRID 746834 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:9]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)=[CH:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[C:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1B(O)O)#[N:21].C(=O)([O-])[O-].[K+].[K+].O>COCCOC.CCOC(C)=O.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.CCCCCC>[F:8][C:6]1[CH:7]=[C:2]([C:23]2[C:22]([C:20]#[N:21])=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:3]=[C:4]([N:9]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)=[CH:10]2)[CH:5]=1

Participants

9

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27346102-Cyanophenylboronic acidHCID 59712247HCID 59712247, compound

Product 1

HCID 11359727HCID 11359727, compoundYield 70.7%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 8058HexaneSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

2-[1-(3-Bromo-5-fluorophenyl)-1H-pyrrol-3-yl]pyridine (647 mg, 2.0 mmol), 2-cyanophenyl boronic acid (300 mg, 2.0 mmol), potassium carbonate (500 mg, 3.0 mmol) were combined in DME:H2O (10:3 mL) under argon and Pd(PPh3)4 (231 mg, 0.2 mmol) was added and the argon flow was continued for 10 min. The reaction mixture was heated at 80° C. overnight. The reaction mixture was allowed to cool to ambient temperature. TLC analysis showed no starting material present. The reaction mixture was diluted with EtOAc (100 mL), and washed with H2O (3×100 mL), brine (100 mL), dried over Na2SO4, filtered, and concentrated in vacuo to afford a dark oil. The crude product was purified by column chromatography eluting with 3.5:6.5 EtOAc:Hexane to afford 3′-fluoro-5′-(3-pyridin-2-yl-1H-pyrrol-1-yl)-1,1′-biphenyl-2-carbonitrile (480 mg, 70% yield) as a yellow solid. 1H NMR (CDCl3, 300 MHz) δ 8.94 (s, 1H), 8.70-8.72 (d, 1H), 8.46-8.49 (t, 1H), 8.33-8.35 (d, 1H), 8.03-8.05 (d, 1H), 7.83-7.95 (m, 4H), 7.79-7.81 (d, 1H), 7.64-7.74 (m, 2H), 7.51-7.53 (d, 1H), 7.40 (s, 1H). MS 340.0 (M++H).

Workup

  1. temperatureto cool to ambient temperature
  2. washwashed with H2O (3×100 mL), brine (100 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto afford a dark oil
  7. customThe crude product was purified by column chromatography
  8. washeluting with 3.5:6.5 EtOAc

Sources & evidence

ORD record
ord-40a186ec2adc4d1ca1023d001de27d03
Source dataset
uspto-grants-2008_07
Patent number
US07393959B2

Reaction notes

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