4-(4-Fluorophenyl)-2-(2-methyl-1-oxopropyl)-4-oxo-3,N-diphenylbutanamide → 5-(4-fluorophenyl)-2-isopropyl-1-(3-morpholin-4-yl-3-oxo-propyl)-4-phenyl-1H-pyrrole-3-carboxylic acid phenylamide

HRID 748589노트

반응식

HRID 748589 반응식
Cl.[NH2:2][CH2:3][CH2:4][C:5]([N:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1)=[O:6].[Na+].C1(CC([O-])=O)C=CC=CC=1.[C:24]1([NH:30][C:31](=[O:54])[CH:32]([CH:38]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[C:39]([C:41]2[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=2)=O)[C:33](=O)[CH:34]([CH3:36])[CH3:35])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1COCC1>[C:24]1([NH:30][C:31]([C:32]2[C:38]([C:48]3[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=3)=[C:39]([C:41]3[CH:42]=[CH:43][C:44]([F:47])=[CH:45][CH:46]=3)[N:2]([CH2:3][CH2:4][C:5]([N:7]3[CH2:12][CH2:11][O:10][CH2:9][CH2:8]3)=[O:6])[C:33]=2[CH:34]([CH3:36])[CH3:35])=[O:54])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

참가 물질

5

반응물 3

HCID 99098724-(4-Fluorophenyl)-2-(2-methyl-1-oxopropyl)-4-oxo-3,N-diphenylbutanamideHCID 162811373-Amino-1-(morpholin-4-yl)propan-1-one hydrochlorideHCID 23690424Sodium Phenylacetate

생성물 1

HCID 111919355-(4-fluorophenyl)-2-isopropyl-1-(3-morpholin-4-yl-3-oxo-propyl)-4-phenyl-1H-pyrrole-3-carboxylic acid phenylamide수율 78%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A nitrogen inerted reactor, equipped with a suitable reflux condenser and soxhlet extractor containing freshly activated 3A molecular sieves (4-8 mesh; 36 g), is charged with 3-amino-1-morpholin-4-yl-propan-1-one hydrochloride (170 mmol), phenylacetic acid sodium salt (170 mmol) and 2-[2-(4-fluorophenyl)-2-oxo-1-phenyl-ethyl]-4-methyl-3-oxo-pentanoic acid phenylamide (100 mmol). THF (150 mL) is added, and the resulting solution is stirred vigorously as the reaction is heated at reflux temperature for ca. 24 hours, during which time the product begins to precipitate. Aqueous NaHCO3 (100 mL) is added slowly, and the reaction mixture is cooled with continued stirring to ca. 0° C. MtBE (100 mL) is added, and the solids are collected via filtration. The yellow-colored solid is washed with distilled water (15 mL) and MtBE (2×15 mL), collected, and dried under vacuum at ≦50° C. to afford 5-(4-fluorophenyl)-2-isopropyl-1-(3-morpholin-4-yl-3-oxo-propyl)-4-phenyl-1H-pyrrole-3-carboxylic acid phenylamide as a white solid (42.1 g). This material is carried on to subsequent steps without further purification.

후처리

  1. customA nitrogen inerted reactor, equipped with a suitable reflux condenser
  2. additionsoxhlet extractor containing freshly
  3. temperatureis heated
  4. temperatureat reflux temperature for ca. 24 hours
  5. customto precipitate
  6. additionAqueous NaHCO3 (100 mL) is added slowly
  7. temperaturethe reaction mixture is cooled
  8. stirringwith continued stirring to ca. 0° C
  9. additionMtBE (100 mL) is added
  10. filtrationthe solids are collected via filtration
  11. washThe yellow-colored solid is washed with distilled water (15 mL) and MtBE (2×15 mL)
  12. customcollected
  13. customdried under vacuum at ≦50° C.

출처 및 근거

ORD 기록
ord-f6e9f7f2dcea4aba8065e58fd531ff91
출처 데이터셋
uspto-grants-2008_07
특허 번호
US07399773B2

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