Methanol → HCID 69303781, compound

HRID 746835Notes

Reaction equation

HRID 746835 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[C:21]1[CH:26]=[CH:25][N:24]=[CH:23][C:22]=1B(O)O.[C:30](=O)([O-])[O-].[K+].[K+].CO>C1(C)C=CC=CC=1.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:21]2[CH:26]=[CH:25][N:24]=[CH:23][C:22]=2[CH3:30])[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 887MethanolHCID 11430Potassium CarbonateHCID 27627114-Methylpyridine-3-Boronic AcidHCID 59712247HCID 59712247, compound

Product 1

HCID 69303781HCID 69303781, compoundYield 59%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

2-[1-(3-Bromo-5-fluorophenyl)-1H-pyrrol-3-yl]pyridine (463 mg, 1.46 mmol), 4-methylpyridin-3-ylboronic acid (200 mg, 1.46 mmol), potassium carbonate (500 mg, 3.0 mmol) were combined in toluene:methanol (10:2 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 90° 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 4-[3-fluoro-5-(3-pyridin-2-yl-1H-pyrrol-1-yl)phenyl]-3-methylpyridine (280 mg, 59% yield) as a yellow solid. 1H NMR (CDCl3, 300 MHz) δ 8.91 (s, 1H), 8.81-8.82 (d, 1H), 8.62-8.63 (d, 2H), 8.51-8.54 (t, 1H), 8.40-8.42 (d, 1H), 8.13-8.15 (d, 1H), 7.75-7.81 (m, 3H), 7.70 (s, 1H), 7.40-7.42 (d, 1H), 7.17 (s, 1H), 2.75 (s, 3H). MS 330.1 (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-1371e620603843b5857ecbff42a77aa2
Source dataset
uspto-grants-2008_07
Patent number
US07393959B2

Reaction notes

Loading…