Sodium t-butoxide → N-[3-[[4-(3-cyano-4-pyrrolidin-1-ylphenyl)pyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide

HRID 1852411Notes

Reaction equation

HRID 1852411 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[CH:10][C:11]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[C:12]([CH:15]=2)[C:13]#[N:14])[CH:5]=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:23]=[C:24]([NH:28][C:29]([N:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)=[O:30])[CH:25]=[CH:26][CH:27]=1.CC([O-])(C)C.[Na+]>O1CCOCC1.O.CCOC(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]>[C:13]([C:12]1[CH:15]=[C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:21][C:22]3[CH:23]=[C:24]([NH:28][C:29]([N:31]4[CH2:35][CH2:34][CH2:33][CH2:32]4)=[O:30])[CH:25]=[CH:26][CH:27]=3)[N:7]=2)[CH:9]=[CH:10][C:11]=1[N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)#[N:14]

Participants

8

Reactant 3

HCID 23676156Sodium t-butoxideHCID 29798917n-(3-Aminophenyl)pyrrolidine-1-carboxamideHCID 866983255-(2-Chloro-pyrimidin-4-yl)-2-pyrrolidin-1-yl-benzonitrile

Product 1

HCID 56646418N-[3-[[4-(3-cyano-4-pyrrolidin-1-ylphenyl)pyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

5-(2-Chloro-pyrimidin-4-yl)-2-pyrrolidin-1-yl-benzonitrile (40 mg, 0.141 mmol), pyrrolidine-1-carboxylic acid (3-amino-phenyl)-amide (29 mg, 0.141 mmol), Pd2(dba)3 (6.4 mg, 0.007 mmol, 5 mol %), 2-dicyclohexylphosphino-2′-(N,N-dimethylaminobiphenyl) (55.5 mg, 0.141 mmol) and NaOtBu (20.3 mg, 0.211 mmol) were dissolved in 1,4-dioxane (1 mL) and the mixture heated at 100° C. in the microwave (300 W, stirring) for 10 minutes. The mixture was diluted with H2O (10 mL) and EtOAc (30 mL) and the layers separated. The aqueous phase was extracted with EtOAc (20 mL) and the combined organics dried (MgSO4), filtered and the solvent evaporated in vacuo. The mixture was dissolved in DMSO (1.5 mL) and the crude product purified by reversed phase preparative LC-MS. Fractions containing desired product were combined and the solvent evaporated in vacuo. The title compound was afforded as a yellow solid (13.1 mg, 21%); LC-MS, Rt=6.50 min (ANALpH2_MeOH_QC), m/z 453 (MH+).

Workup

  1. customthe layers separated
  2. extractionThe aqueous phase was extracted with EtOAc (20 mL)
  3. dry with materialthe combined organics dried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent evaporated in vacuo
  6. dissolutionThe mixture was dissolved in DMSO (1.5 mL)
  7. customthe crude product purified by reversed phase preparative LC-MS
  8. additionFractions containing desired product
  9. customthe solvent evaporated in vacuo

Sources & evidence

ORD record
ord-41334ddd463b42ab9ef62cbb8700000e
Source dataset
uspto-grants-2015_02
Patent number
US08962609B2

Reaction notes

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