Phenylacetic Acid → 5-(4-fluorophenyl)-2-isopropyl-1-(3-morpholin-4-yl-3-oxo-propyl)-4-phenyl-1H-pyrrole-3-carboxylic acid phenylamide

HRID 351456노트

반응식

HRID 351456 반응식
[NH2:1][CH2:2][CH2:3][C:4]([N:6]1[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1)=[O:5].C1(CC(O)=O)C=CC=CC=1.[C:22]1([NH:28][C:29](=[O:52])[CH:30]([CH:36]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:37]([C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=2)=O)[C:31](=O)[CH:32]([CH3:34])[CH3:33])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1COCC1>[C:22]1([NH:28][C:29]([C:30]2[C:36]([C:46]3[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=3)=[C:37]([C:39]3[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=3)[N:1]([CH2:2][CH2:3][C:4]([N:6]3[CH2:11][CH2:10][O:9][CH2:8][CH2:7]3)=[O:5])[C:31]=2[CH:32]([CH3:34])[CH3:33])=[O:52])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

참가 물질

5

반응물 3

HCID 999Phenylacetic AcidHCID 65042503-Amino-1-(morpholin-4-yl)propan-1-oneHCID 99098724-(4-Fluorophenyl)-2-(2-methyl-1-oxopropyl)-4-oxo-3,N-diphenylbutanamide

생성물 1

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

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; 97.2 g), is charged with 3-amino-1-morpholin-4-yl-propan-1-one, compound with phenylacetic acid (765 mmol) and 2-[2-(4-fluorophenyl)-2-oxo-1-phenyl-ethyl]-4-methyl-3-oxo-pentanoic acid phenylamide (450 mmol). THF (360 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. Half-saturated aqueous NaHCO3 (100 mL) is added, 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 solid is washed with distilled water (100 mL) and MtBE (2×100 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 (194 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. additionHalf-saturated aqueous NaHCO3 (100 mL) is added
  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 solid is washed with distilled water (100 mL) and MtBE (2×100 mL)
  12. customcollected
  13. customdried under vacuum at <50° C.

출처 및 근거

ORD 기록
ord-0cef5dcfe9dd4520a861542a2effa154
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07183408B2

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