Potassium Carbonate → HCID 59631205, compound

HRID 1431423Notes

Reaction equation

HRID 1431423 reaction equation
[NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][C:2]1=[O:7].Cl[C:9]1[C:18]([CH3:19])=[C:17]([Cl:20])[C:16]2[C:11](=[CH:12][C:13]([F:22])=[CH:14][C:15]=2[F:21])[N:10]=1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>CC(O)(C)C.O.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.[Pd].[Pd]>[Cl:20][C:17]1[C:16]2[C:11](=[CH:12][C:13]([F:22])=[CH:14][C:15]=2[F:21])[N:10]=[C:9]([N:4]2[CH2:5][CH2:6][NH:1][C:2](=[O:7])[CH2:3]2)[C:18]=1[CH3:19]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 231360Piperazin-2-oneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596310402,4-Dichloro-5,7-difluoro-3-methylquinoline

Product 1

HCID 59631205HCID 59631205, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

The piperazin-2-one (161 mg, 1.613 mmol) and 2,4-dichloro-5,7-difluoro-3-methylquinoline (400.0 mg, 1.613 mmol) were dissolved in t-BuOH (7.00 mL) and heated in the microwave at 100° C. for 30 min. Only a trace amount of product present. Potassium carbonate (557 mg, 4.03 mmol) was added and the mixture heated in the microwave at 100° C. for 45 min. Again, only a trace amount of product was observed. The 2-(dicyclohexylphosphino)-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (123 mg, 0.258 mmol) and Pd2(dba)3 (59.1 mg, 0.065 mmol) was then added and the mixture was stirred in the microwave at 120° C. for 4 h. The reaction was then diluted with water (˜50 mL) and the mixture was extracted with EtOAc (1×100 mL), DCM (1×100 mL) and 10% MeOH:DCM (1×100 mL). The combined organic layers were dried over magnesium sulfate and the crude product was purified by medium pressure chromatography (silica, 0 to 10% 2M ammonia in MeOH:DCM) to give 4-(4-chloro-5,7-difluoro-3-methylquinolin-2-yl)piperazin-2-one. Mass Spectrum (ESI) m/e=312.1 (M+1).

Workup

  1. temperaturethe mixture heated in the microwave at 100° C. for 45 min
  2. extractionthe mixture was extracted with EtOAc (1×100 mL), DCM (1×100 mL) and 10% MeOH
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. customthe crude product was purified by medium pressure chromatography (silica, 0 to 10% 2M ammonia in MeOH:DCM)

Sources & evidence

ORD record
ord-558225ba7d324159806a91f211f86083
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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