Pyridine → 1-cyano-N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)cyclopropanecarboxamide

HRID 1049331Notes

Reaction equation

HRID 1049331 reaction equation
[C:1]([C:3]1([C:6]([NH2:8])=[O:7])[CH2:5][CH2:4]1)#[N:2].C(Cl)(=O)[C:10](Cl)=[O:11].[CH3:15][N:16]1[CH:20]=[C:19]([C:21]2[CH:26]=[C:25]([O:27][C:28]3[CH:29]=[CH:30][C:31]([NH2:34])=[N:32][CH:33]=3)[CH:24]=[CH:23][N:22]=2)[CH:18]=[N:17]1.N1C=CC=CC=1>ClCCCl.C1COCC1>[C:1]([C:3]1([C:6]([NH:8][C:10](=[O:11])[NH:34][C:31]2[CH:30]=[CH:29][C:28]([O:27][C:25]3[CH:24]=[CH:23][N:22]=[C:21]([C:19]4[CH:18]=[N:17][N:16]([CH3:15])[CH:20]=4)[CH:26]=3)=[CH:33][N:32]=2)=[O:7])[CH2:5][CH2:4]1)#[N:2]

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 142008551-Cyanocyclopropane-1-carboxamideHCID 593227775-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amine

Product 1

HCID 862680671-cyano-N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)cyclopropanecarboxamideYield 78%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of Example B8 (0.074 g, 0.673 mmol) in DCE (4 mL) was treated with oxalyl chloride (0.059 mL, 0.673 mmol), stirred at RT for 1 h, then heated to 80° C. for 1.5 h. The mixture was cooled to RT, added drop-wise to a solution of Example A2 (0.15 g, 0.561 mmol) and pyridine (0.226 mL, 2.81 mmol) in THF (4 mL) and stirred at RT overnight. The mixture was treated with satd. NaHCO3, extracted with EtOAc (4×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford 1-cyano-N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)cyclopropanecarboxamide (176 mg, 78%) as an off-white solid. MS (ESI) m/z: 404.1 (M+H+).

Workup

  1. temperatureheated to 80° C. for 1.5 h
  2. temperatureThe mixture was cooled to RT
  3. stirringstirred at RT overnight
  4. additionThe mixture was treated with satd
  5. extractionNaHCO3, extracted with EtOAc (4×)
  6. dry with materialthe combined organics were dried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-41cfc4e58c7647c6900fae1236df8154
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

Loading…