N-methyl-2-pyrrolidone → 7-Bromo-1-cyano-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester

HRID 1481173Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8](I)[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([Br:17])[CH:10]=2)=[O:5])[CH3:2].[CH3:19][N:20]1C(=O)CCC1>ClCCl>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C:19]#[N:20])[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([Br:17])[CH:10]=2)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 120 °C

Procedure

7-Bromo-4-hydroxy-1-iodo-isoquinoline-3-carboxylic acid ethyl ester (1.0 g, 2.37 mmol) was dissolved in anhydrous NMP and cuprous cyanide was added (255 mg, 2.844 mmol) was added as a solid in one portion. The solution was heated to 120° C. in an oil bath. Upon completion, the reaction was cooled, diluted with 15 volumes of dichloromethane and stirred overnight. The following day the solution was washed with 1M hydrochloric acid, water, then brine and dried over sodium sulfate. The crude material was purified by medium pressure liquid chromatography (20 to 75% ethyl acetate in hexanes) to give the desired material in 85% yield as tan solid. 1H NMR (200 MHz, CDCl3): δ ppm=12.48 (s, 1H), 8.46 (s, 1H), 8.32 (d, 1H), 7.94 (d, 1H), 4.59 (q, 2H), 1.53 (t, 3H.)

Workup

additionwas added as a solid in one portion
temperatureUpon completion, the reaction was cooled
washThe following day the solution was washed with 1M hydrochloric acid, water
dry with materialbrine and dried over sodium sulfate
customThe crude material was purified by medium pressure liquid chromatography (20 to 75% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-afdf3dac58dc45a286759a9099f82129
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409892B2

Reaction notes

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