Cesium carbonate → 3-cyclopropyl-1-(2-((1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrile

HRID 714898Notes

Reaction equation

HRID 714898 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]([C:14]([CH3:18])([CH3:17])[CH2:15][OH:16])[CH:13]=2)[N:3]=1.[CH:19]1([C:22]2([C:28]#[N:29])[CH2:26][CH2:25][NH:24][C:23]2=[O:27])[CH2:21][CH2:20]1.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>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:19]1([C:22]2([C:28]#[N:29])[CH2:26][CH2:25][N:24]([C:2]3[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]4[CH:10]=[N:11][N:12]([C:14]([CH3:18])([CH3:17])[CH2:15][OH:16])[CH:13]=4)[N:3]=3)[C:23]2=[O:27])[CH2:21][CH2:20]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 916186313-Cyclopropyl-2-oxopyrrolidine-3-carbonitrileHCID 1178401582-(4-((4-chloropyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-2-methylpropan-1-ol

Product 1

HCID 781662193-cyclopropyl-1-(2-((1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrileYield 46.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of 2-(4-((4-chloropyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-2-methylpropan-1-ol (200 mg) obtained in Step E of Example 347, 3-cyclopropyl-2-oxopyrrolidine-3-carbonitrile (110 mg) obtained in Step C of Example 103, cesium carbonate (490 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (26 mg) in toluene (2.0 mL) was added tris(dibenzylideneacetone)dipalladium(0) (14 mg), and the mixture was stirred overnight at 85° 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) to give the title compound (130 mg).

Workup

  1. customThe insoluble substance was removed by filtration through Celite
  2. customthe solvent was evaporated under reduced pressure
  3. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-b78e2e740bd84ac1beb6bd495211c093
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

Loading…