Cesium carbonate → tert-butyl 4-((4-((3S)-3-cyano-3-cyclopropyl-2-oxopyrrolidin-1-yl) pyrimidin-2-yl)amino)-2-ethoxybenzoate

HRID 714854Notes

Reaction equation

HRID 714854 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][C@:10]([CH:15]3[CH2:17][CH2:16]3)([C:13]#[N:14])[C:9]2=[O:18])[CH:5]=[CH:4][N:3]=1.[NH2:19][C:20]1[CH:32]=[CH:31][C:23]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[C:22]([O:33][CH2:34][CH3:35])[CH:21]=1.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]>[C:13]([C@@:10]1([CH:15]2[CH2:17][CH2:16]2)[CH2:11][CH2:12][N:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:19][C:20]3[CH:32]=[CH:31][C:23]([C:24]([O:26][C:27]([CH3:29])([CH3:30])[CH3:28])=[O:25])=[C:22]([O:33][CH2:34][CH3:35])[CH:21]=3)[N:7]=2)[C:9]1=[O:18])#[N:14]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 117840203(3S)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-2-oxopyrrolidine-3-carbonitrileHCID 117840502Tert-butyl 4-amino-2-ethoxybenzoate

Product 1

HCID 117841126tert-butyl 4-((4-((3S)-3-cyano-3-cyclopropyl-2-oxopyrrolidin-1-yl) pyrimidin-2-yl)amino)-2-ethoxybenzoateYield 23.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (3S)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-2-oxopyrrolidine-3-carbonitrile (100 mg) obtained in Step E of Example 103, tert-butyl 4-amino-2-ethoxybenzoate (110 mg) obtained in Step C of Example 139, cesium carbonate (250 mg) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (35 mg) in tetrahydrofuran (3.0 mL) was added tris(dibenzylideneacetone)dipalladium(0) (34 mg) under argon atmosphere, 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) to give the title compound (41 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-770608cfc2474c21a9b4962eb39642ca
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

Loading…