2-Fluoroaniline → 7-fluoro-6-(2-fluorophenylamino)-3-methyl-3H-imidazo[4,5-b]pyridine-5-carboxylic acid methyl ester

HRID 2102397Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[N:10]=[C:9]2[N:11]([CH3:14])[CH:12]=[N:13][C:8]2=[C:7]([F:15])[C:6]=1Br)=[O:4].[F:17][C:18]1[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=1[NH2:20].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:2][C:3]([C:5]1[N:10]=[C:9]2[N:11]([CH3:14])[CH:12]=[N:13][C:8]2=[C:7]([F:15])[C:6]=1[NH:20][C:19]1[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=1[F:17])=[O:4]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 6-bromo-7-fluoro-3-methyl-3H-imidazo[4,5-b]pyridine-5-carboxylic acid methyl ester (1.00 equivalent), 2-fluoroaniline (1.00 equivalent), Pd(OAc)2 (0.10 equivalents), rac-BINAP (0.15 equivalents), and Cs2CO3 (1.50 equivalents) in toluene in a sealed tube is stirred at 80° C. for 16 hours. The reaction mixture is cooled to room temperature and diluted with EtOAc. The resulting precipitate is filtered off and washed with EtOAc. The filtrate is diluted with EtOAc and washed with water. The organic layer is dried over MgSO4, filtered, and concentrated in vacuo to give the crude material that is purified by trituration or flash column chromatography to afford the desired product.

Workup

temperatureThe reaction mixture is cooled to room temperature
filtrationThe resulting precipitate is filtered off
washwashed with EtOAc
additionThe filtrate is diluted with EtOAc
washwashed with water
dry with materialThe organic layer is dried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customto give the crude material that
customis purified by trituration or flash column chromatography

Sources & evidence

ORD record: ord-c1e70a0272e64146bc027045cd372019
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07576072B2

Reaction notes

Loading…