4-[2-cyclopentyl-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-vinyl]-2-fluoro-benzoic acid methyl ester → 4-[2-cyclopentyl-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-ethyl]-2-fluoro-benzoic acid methyl ester

HRID 1515840Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([C:17]2[NH:26][C:20]3=[N:21][CH:22]=[C:23]([F:25])[CH:24]=[C:19]3[CH:18]=2)=[CH:11][CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)=[CH:6][C:5]=1[F:27]>[Pd].CO>[CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([CH:10]([C:17]2[NH:26][C:20]3=[N:21][CH:22]=[C:23]([F:25])[CH:24]=[C:19]3[CH:18]=2)[CH2:11][CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16]2)=[CH:6][C:5]=1[F:27]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 4-[2-cyclopentyl-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-vinyl]-2-fluoro-benzoic acid methyl ester (1.50 g, 3.93 mmol) and 10% palladium on activated carbon (300 mg) in methanol (300 mL) was heated at 50° C. under hydrogen (50 psi) for 5 h. The mixture was cooled to 25° C., the solids filtered off, washed with ethyl acetate and concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 20% ethyl acetate/hexanes) afforded 4-[2-cyclopentyl-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-ethyl]-2-fluoro-benzoic acid methyl ester (1.40 g, 92%): LC/MS m/e calcd for C22H22F2N2O2 [M+H]+ 385.43, observed 384.9.

Workup

temperatureThe mixture was cooled to 25° C.
filtrationthe solids filtered off
washwashed with ethyl acetate
concentrationconcentrated in vacuo
customPurification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 20% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-85abb6fb22a14387924093100617a81e
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08222416B2

Reaction notes

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