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

HRID 1481168노트

반응식

HRID 1481168 반응식
[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]

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
120 °C

실험 절차

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.)

후처리

  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)

출처 및 근거

ORD 기록
ord-eb735c68fc944c1e904b97da5d67f00b
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409892B2

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