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

HRID 1016730Notes

Reaction equation

HRID 1016730 reaction equation
[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

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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.

Sources & evidence

ORD record
ord-0263cdd2fda24fa08a7096556d81ce35
Source dataset
uspto-grants-2002_11
Patent number
US06476235B2

Reaction notes

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