Sodium hydride → 2-Fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)aniline

HRID 2117175Notes

Reaction equation

Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][CH:9]=[CH:10][C:3]=12.[NH2:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][C:13]=1[F:19].CCN(C(C)C)C(C)C.[H-].[Na+]>CN1C(=O)CCC1.O>[NH:8]1[C:4]2=[N:5][CH:6]=[CH:7][C:2]([O:18][C:15]3[CH:16]=[CH:17][C:12]([NH2:11])=[C:13]([F:19])[CH:14]=3)=[C:3]2[CH:10]=[CH:9]1

Participants

Conditions

Temperature: 250 °C

Procedure

To a solution of 4-chloro-1H-pyrrolo[2,3-b]pyridine (50 mg, 0.33 mmol, prepared according to Thibault, C. et al. Org. Lett. 2003, 5, 5023) in NMP (0.5 mL) were added 4-amino-3-fluorophenol (51 mg, 0.40 mmol) and DIEA (0.1 mL, 0.57 mmol). The mixture was heated at 250° C. in a microwave oven for 1 h and then cooled to room temperature. To the mixture was added NaH (10 mg, 0.4 mmol) and the mixture was again heated at 250° C. for 3 h. After cooling, the mixture was diluted with H2O and extracted with EtOAc. The organic layer was washed with H2O, brine, and dried over MgSO4. After filtration and concentration in vacuo, the residue was purified by flash column chromatography (ISCO RediSep® silica gel cartridge) to give the title compound (15 mg, 19%). MS (ESI) m/z 244.1 (M+H)+.

Workup

temperaturecooled to room temperature
temperaturethe mixture was again heated at 250° C. for 3 h
temperatureAfter cooling
extractionextracted with EtOAc
washThe organic layer was washed with H2O, brine
dry with materialdried over MgSO4
filtrationAfter filtration and concentration in vacuo
customthe residue was purified by flash column chromatography (ISCO RediSep® silica gel cartridge)

Sources & evidence

ORD record: ord-56f858d9c8bb4550896d9a31b8f5fa4a
Source dataset: uspto-grants-2008_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07439246B2

Reaction notes

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