2-Pyrrolidone → HCID 71252650, compound

HRID 2411988Notes

Reaction equation

HRID 2411988 reaction equation
[C:1]([N:4]1[CH2:8][CH2:7][N:6]([C:9]2[CH:14]=[C:13](Cl)[CH:12]=[CH:11][C:10]=2[C:16]([N:18]2[CH2:23][CH2:22][N:21]([C:24]3[C:29]([CH3:30])=[CH:28][C:27]([CH3:31])=[CH:26][N:25]=3)[CH2:20][CH2:19]2)=[O:17])[C:5]1=[O:32])(=[O:3])[CH3:2].[NH:33]1[CH2:37][CH2:36][CH2:35][C:34]1=[O:38].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd].O.C(O)(C)(C)C>[C:1]([N:4]1[CH2:8][CH2:7][N:6]([C:9]2[CH:14]=[C:13]([N:33]3[CH2:37][CH2:36][CH2:35][C:34]3=[O:38])[CH:12]=[CH:11][C:10]=2[C:16]([N:18]2[CH2:23][CH2:22][N:21]([C:24]3[C:29]([CH3:30])=[CH:28][C:27]([CH3:31])=[CH:26][N:25]=3)[CH2:20][CH2:19]2)=[O:17])[C:5]1=[O:32])(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 120252-PyrrolidoneHCID 62657Potassium Phosphate, TribasicHCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphaneHCID 584846831-Acetyl-3-{5-chloro-2-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]phenyl}imidazolidin-2-one

Product 1

HCID 71252650HCID 71252650, compound

Reagents, catalysts & solvents 3

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 962WaterSolventHCID 6386tert-ButanolSolvent

Procedure

To a mixture of 1-acetyl-3-{5-chloro-2-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]phenyl}imidazolidin-2-one (228 mg) described in Preparation Example 234, pyrrolidin-2-one (64 mg), tripotassium phosphate (149 mg), tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (52 mg) and 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2′,4′,6′-triisopropyl-1,1′-biphenyl (24 mg) was added tert-butanol (1.5 mL), and the mixture was stirred with heating under reflux for 8 hr. The reaction mixture was cooled, water was added, and the mixture was extracted with ethyl acetate. The solvent was evaporated and methanol (1.6 mL), 1N aqueous sodium hydroxide solution (0.75 mL) were added to the obtained crude product of 1-acetyl-3-[2-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-5-(2-oxopyrrolidin-1-yl)phenyl}imidazolidin-2-one, and the mixture was stirred at 40° C. for 3 hr. After cooling, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The solvent was evaporated, and the residue was purified by column chromatography (ethyl acetate:methanol) to give the title compound (69 mg).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 8 hr
  3. temperatureThe reaction mixture was cooled
  4. extractionthe mixture was extracted with ethyl acetate
  5. customThe solvent was evaporated
  6. additionmethanol (1.6 mL), 1N aqueous sodium hydroxide solution (0.75 mL) were added to the

Sources & evidence

ORD record
ord-0f7829100fbe43fbb7561ba68671a48a
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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