Isobutylamine → {(1S,2S,4S)-4-Isobutylcarbamoyl-1-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl ester

HRID 1694949노트

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HRID 1694949 반응식
[CH2:1]([NH2:5])[CH:2]([CH3:4])[CH3:3].OC1C=CC=CN=1.[C:13]([O:17][C:18](=[O:48])[NH:19][C@H:20]([C@@H:39]1[CH2:43][C@@H:42]([CH:44]([CH3:46])[CH3:45])[C:41](=[O:47])[O:40]1)[CH2:21][N:22]1[CH2:27][C:26](=[O:28])[N:25]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=2[CH3:36])[CH2:24][C:23]1([CH3:38])[CH3:37])([CH3:16])([CH3:15])[CH3:14]>O>[C:13]([O:17][C:18](=[O:48])[NH:19][C@@H:20]([CH2:21][N:22]1[CH2:27][C:26](=[O:28])[N:25]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=2[CH3:36])[CH2:24][C:23]1([CH3:38])[CH3:37])[C@@H:39]([OH:40])[CH2:43][C@H:42]([C:41](=[O:47])[NH:5][CH2:1][CH:2]([CH3:4])[CH3:3])[CH:44]([CH3:46])[CH3:45])([CH3:14])([CH3:16])[CH3:15]

참가 물질

5

반응물 3

HCID 6558IsobutylamineHCID 66645725{(S)-2-[2,2-Dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl esterHCID 178516071HCID 178516071, 화합물

생성물 1

HCID 66645880{(1S,2S,4S)-4-Isobutylcarbamoyl-1-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl ester수율 100.1%

시약·촉매·용매 1

HCID 962Water용매

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온도
80 °C

실험 절차

0.4 ml of isobutylamine (3.96 mmol) and 8 mg of 2-hydroxypyridine (0.079 mmol) were added to 200 mg of {(S)-2-[2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl ester obtained in Example (70f) (0.39 mmol), and the mixture was stirred at 80° C. for four hours. The reaction mixture was cooled and then water was added, followed by extraction with ethyl acetate. Then, the organic layer was washed with brine and then dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=20/1) to obtain 226 mg of the title compound (yield: 99%).

후처리

  1. temperatureThe reaction mixture was cooled
  2. extractionfollowed by extraction with ethyl acetate
  3. washThen, the organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationAfter filtration
  6. customthe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=20/1)

출처 및 근거

ORD 기록
ord-c153931bd8654bbf88ecc8f8d8a71631
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08158790B2

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