2-Methyl-1H-pyrrolo(2,3-c)pyridine → 2-(1-fluorocyclopropyl)-4-(5-fluoro-2-methoxyphenyl)-4-methyl-1-(1H-pyrrolo[2,3-c]pyridin-2-yl)pentan-2-ol

HRID 400685Notes

Reaction equation

HRID 400685 reaction equation
[CH3:1][C:2]1[NH:10][C:5]2=[CH:6][N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=1.[Li]CCCC.C(O[K])(C)(C)C.[F:22][C:23]1([C:26](=[O:40])[CH2:27][C:28]([C:31]2[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=2[O:38][CH3:39])([CH3:30])[CH3:29])[CH2:25][CH2:24]1>C1COCC1.C(OCC)(=O)C>[F:22][C:23]1([C:26]([OH:40])([CH2:27][C:28]([C:31]2[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=2[O:38][CH3:39])([CH3:30])[CH3:29])[CH2:1][C:2]2[NH:10][C:5]3=[CH:6][N:7]=[CH:8][CH:9]=[C:4]3[CH:3]=2)[CH2:24][CH2:25]1

Participants

7

Reactant 4

HCID 124075052-Methyl-1H-pyrrolo(2,3-c)pyridineHCID 600267971-(1-Fluorocyclopropyl)-3-(5-fluoro-2-methoxyphenyl)-3-methylbutan-1-oneHCID 178418339ButyllithiumHCID 178418922HCID 178418922, compound

Product 1

HCID 114181582-(1-fluorocyclopropyl)-4-(5-fluoro-2-methoxyphenyl)-4-methyl-1-(1H-pyrrolo[2,3-c]pyridin-2-yl)pentan-2-olYield 45%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-methyl-1H-pyrrolo[2,3-c]pyridine (80.0 mg, 0.605 mmol) in 2 mL of THF cooled to −78° C. was added 0.70 mL of n-BuLi (1.6 M in hexanes). After 5 minutes, tert-BuOK (1 M in THF, 0.75 mL) was added and the mixture was warmed to room temperature for 1 hour. The mixture was cooled to −78° C. and the above 1-(1-fluorocyclopropyl)-3-(5-fluoro-2-methoxyphenyl)-3-methylbutan-1-one (150 mg, 0.600 mmol) was added as a solution in 0.5 mL of THF. The mixture was stirred for 30 minutes at −78° C. and warmed to room temperature. 5 mL of ethyl acetate was added and the organic phase was washed with water, dried, filtered, and evaporated. Preparative layer chromatography (developer: dichloromethane-ethanol (95:5)) gave 100 mg of the title compound as an oil that solidified on standing (45% yield).

Workup

  1. temperatureThe mixture was cooled to −78° C.
  2. temperaturewarmed to room temperature
  3. washthe organic phase was washed with water
  4. customdried
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-1c8bc11dcd5c42c294cdaa642457c6cc
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

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