N-[6-(3-aminophenoxy)[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide → 3-(1-cyanocyclopropyl)-N-[3-({2-[(cyclopropylcarbonyl)amino][1,2,4]triazolo[1,5-a]pyridin-6-yl}oxy)phenyl]benzamide

HRID 1874585

Reaction equation

HRID 1874585 reaction equation
[C:1]([C:3]1([C:6]2[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=2)[C:9](Cl)=[O:10])[CH2:5][CH2:4]1)#[N:2].[NH2:15][C:16]1[CH:17]=[C:18]([CH:35]=[CH:36][CH:37]=1)[O:19][C:20]1[CH:21]=[CH:22][C:23]2[N:24]([N:26]=[C:27]([NH:29][C:30]([CH:32]3[CH2:34][CH2:33]3)=[O:31])[N:28]=2)[CH:25]=1>CN(C)C(=O)C.C(OCC)(=O)C>[C:1]([C:3]1([C:6]2[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=2)[C:9]([NH:15][C:16]2[CH:37]=[CH:36][CH:35]=[C:18]([O:19][C:20]3[CH:21]=[CH:22][C:23]4[N:24]([N:26]=[C:27]([NH:29][C:30]([CH:32]5[CH2:33][CH2:34]5)=[O:31])[N:28]=4)[CH:25]=3)[CH:17]=2)=[O:10])[CH2:5][CH2:4]1)#[N:2]

Participants

5

Reactant 2

HCID 57749117N-[6-(3-aminophenoxy)[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamideHCID 866319823-(1-Cyanocyclopropyl)benzoyl chloride

Product 1

HCID 577491263-(1-cyanocyclopropyl)-N-[3-({2-[(cyclopropylcarbonyl)amino][1,2,4]triazolo[1,5-a]pyridin-6-yl}oxy)phenyl]benzamideYield 63%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 3-(1-cyanocyclopropyl)benzoyl chloride synthesized above in N,N-dimethylacetamide (5.0 mL) was added N-[6-(3-aminophenoxy)[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide (150 mg, 0.485 mmol), and the mixture was stirred at room temperature for 8 hr. The reaction mixture was diluted with ethyl acetate (100 mL), washed with 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=60/40→0/100), and the obtained oil was triturated with ethyl acetate, toluene and diisopropyl ether to give the title compound (175 mg, 63%) as a colorless powder.

Workup

  1. washwashed with 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationThe insoluble material was filtered off
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=60/40→0/100)
  6. customthe obtained oil was triturated with ethyl acetate, toluene and diisopropyl ether

Sources & evidence

ORD record
ord-18721e472ac345ee962ef7b970f295dc
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Linked notes

Loading…