Cesium carbonate → 3-ethyl-1-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrile

HRID 714780Notes

Reaction equation

Cl[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([C:23]#[N: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)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=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]>[CH2:15]([C:17]1([C:23]#[N: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: 90 °C

Procedure

To a mixture of 4-chloro-N-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-amine (110 mg) obtained in Step C, 3-ethyl-2-oxopyrrolidine-3-carbonitrile (82 mg) obtained in Step H, cesium carbonate (350 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (19 mg) in tetrahydrofuran (3 mL) was added tris(dibenzylideneacetone)dipalladium(0) (10 mg), and the mixture was stirred overnight at 90° C. 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), and recrystallized (hexane/ethyl acetate) to give the title compound (87 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)
customrecrystallized (hexane/ethyl acetate)

Sources & evidence

ORD record: ord-13421e7344b741888ca81bb81e5b8dbc
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187453B2

Reaction notes

Loading…