Pyridine → N-(5-Fluoro-2-oxo-2,3-dihydro-1H-indol-6-yl)-2-methoxyacetamide

HRID 2191413Notes

Reaction equation

[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][C:3]=1[F:12].N1C=CC=CC=1.[CH3:19][O:20][CH2:21][C:22](Cl)=[O:23]>O1CCCC1>[F:12][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:2]=1[NH:1][C:22](=[O:23])[CH2:21][O:20][CH3:19])[NH:8][C:7](=[O:11])[CH2:6]2

Participants

Conditions

Temperature: -50 °C

Procedure

6-Amino-5-fluoro-1,3-dihydro-indol-2-one 3d (2.028 g, 12.2 mmol) was dissolved in 30 ml of tetrahydrofuran under stirring, and added with 1.3 ml of pyridine to the solution at room temperature. The reaction system was cooled down to about −50° C. in a dry ice-ethanol bath. A solution of methoxy-acetyl chloride (1.35 g, 12.5 mmol) in tetrahydrofuran (20 ml) was added dropwise to the above reaction system. Upon completion of the addition, the ice-ethanol bath was removed, and the reaction mixture was allowed to warm up to room temperature and stirred overnight. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was filtered. The resulting solid was washed with water (10 mL×3) and recrystallized with methanol to obtain N-(5-fluoro-2-oxo-2,3-dihydro-1H-indol-6-yl)-2-methoxy-acetamide 7a (1.18 mg, yield 40.6%) as a gray solid.

Workup

additionUpon completion of the addition
customthe ice-ethanol bath was removed
temperatureto warm up to room temperature
stirringstirred overnight
filtrationthe reaction mixture was filtered
washThe resulting solid was washed with water (10 mL×3)
customrecrystallized with methanol

Sources & evidence

ORD record: ord-41c5baff3792400c960605bd6a53dc34
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329682B2

Reaction notes

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