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Water → {(1S,2S,4R)-4-(Cyclohexylcarbamoyl)-1-[4-(2,6-difluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxypentyl}carbamic acid t-butyl ester

HRID 1694973
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HRID 1694973 반응식
OC1C=CC=CN=1.[C:8]([O:12][C:13](=[O:41])[NH:14][C@H:15]([C@@H:34]1[CH2:38][C@@H:37]([CH3:39])[C:36](=[O:40])[O:35]1)[CH2:16][N:17]1[CH2:22][C:21](=[O:23])[N:20]([C:24]2[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=2[F:31])[CH2:19][C:18]1([CH3:33])[CH3:32])([CH3:11])([CH3:10])[CH3:9].O.[CH:43]1([NH2:49])[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]1>>[C:8]([O:12][C:13](=[O:41])[NH:14][C@@H:15]([CH2:16][N:17]1[CH2:22][C:21](=[O:23])[N:20]([C:24]2[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=2[F:31])[CH2:19][C:18]1([CH3:33])[CH3:32])[C@@H:34]([OH:35])[CH2:38][C@H:37]([C:36](=[O:40])[NH:49][CH:43]1[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]1)[CH3:39])([CH3:11])([CH3:9])[CH3:10]
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참가 물질

5

반응물 4

HCID 962WaterHCID 7965CyclohexylamineHCID 66645687{(S)-2-[4-(2,6-Difluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl esterHCID 178516071HCID 178516071, 화합물

생성물 1

HCID 66645507{(1S,2S,4R)-4-(Cyclohexylcarbamoyl)-1-[4-(2,6-difluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxypentyl}carbamic acid t-butyl ester
수율 88%

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온도
80 °C

실험 절차

7.9 mg of 2-hydroxypyridine (0.08 mmol) was added to a solution of 200 mg of {(S)-2-[4-(2,6-difluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl ester obtained in Example (93b) (0.41 mmol) in cyclohexylamine (1.0 ml), and the mixture was stirred at 80° C. for three hours. The reaction mixture was cooled and then water was added, followed by extraction with methylene chloride. Then, the organic layer was dried over anhydrous magnesium 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 218 mg of the title compound (yield: 88%).

후처리

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

출처 및 근거

ORD 기록
ord-4541223629fc4a41871b193f98e88ab5
출처 데이터셋
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08158790B2

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