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

HRID 1481173ノート

反応式

HRID 1481173 の反応式
[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]

参加物

4

反応物 2

HCID 13387N-methyl-2-pyrrolidoneHCID 89812910Ethyl 7-bromo-4-hydroxy-1-iodo-3-isoquinolinecarboxylate

生成物 1

HCID 898128697-Bromo-1-cyano-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester収率 85%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
120 °C

実験手順

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.)

後処理

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

出典と根拠

ORDレコード
ord-afdf3dac58dc45a286759a9099f82129
出典データセット
uspto-grants-2016_08
特許番号
US09409892B2

反応ノート

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