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

HRID 1852411Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1852411
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]

Komponenten

8

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

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+).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-41334ddd463b42ab9ef62cbb8700000e
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08962609B2

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