Cesium carbonate → 3,3-diethyl-1-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)pyrrolidin-2-one hydrochloride

HRID 714795Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=2)[N:3]=1.[CH2:15]([C:17]1([CH2:23][CH3:24])[CH2:21][CH2:20][NH:19][C:18]1=[O:22])[CH3:16].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1.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]>[ClH:1].[CH2:15]([C:17]1([CH2:23][CH3:24])[CH2:21][CH2:20][N:19]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]3[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=3)[N:3]=2)[C:18]1=[O:22])[CH3:16]

Participants

Conditions

Temperature: 130 °C

Procedure

To a mixture of 4-chloro-N-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-amine (150 mg) obtained in Step C of Example 1, 3,3-diethylpyrrolidin-2-one (110 mg), cesium carbonate (700 mg) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (90 mg) in tetrahydrofuran (5 mL) was added tris(dibenzylideneacetone)dipalladium(0) (130 mg), and the mixture was stirred in a microwave reactor at 130° C. for 1.5 hr. The insoluble substance was removed by filtration through Celite, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate), to a solution of the residue in ethanol (5 mL) was added 12M hydrogen chloride ethanol solution (1 mL), and the mixture was stirred at room temperature for 5 min. The solvent was evaporated under reduced pressure, and the obtained crude crystals were recrystallized (ethanol/ethyl acetate) to give the title compound (76 mg).

Workup

customThe insoluble substance was removed by filtration through Celite
customthe solvent was evaporated under reduced pressure
customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate), to a solution of the residue in ethanol (5 mL)
additionwas added 12M hydrogen chloride ethanol solution (1 mL)
stirringthe mixture was stirred at room temperature for 5 min
customThe solvent was evaporated under reduced pressure
customthe obtained crude crystals
customwere recrystallized (ethanol/ethyl acetate)

Sources & evidence

ORD record: ord-0b2b41d9fea842f8a23c0a95528bf8cd
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187453B2

Reaction notes

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