Oxalyl chloride → N-(3-Ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79272

Reaction equation

HRID 79272 reaction equation
[N:1]1[CH:2]=[C:3]([C:10]([OH:12])=O)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.C(Cl)(=O)C(Cl)=O.C(N(C(C)C)CC)(C)C.[CH2:28]([C:30]1[C:38]2[C:37]([NH2:39])=[CH:36][CH:35]=[CH:34][C:33]=2[N:32]([CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([CH3:47])[N:42]=2)[N:31]=1)[CH3:29]>ClCCl.CN(C)C=O>[CH2:28]([C:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][C:37]=2[NH:39][C:10]([C:3]2[N:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]3=[N:1][CH:2]=2)=[O:12])[N:32]([CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([CH3:47])[N:42]=2)[N:31]=1)[CH3:29]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 73142Imidazo(1,2-a)pyridine-3-carboxylic acidHCID 81531DiisopropylethylamineHCID 672598043-ethyl-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amine

Product 1

HCID 67259302N-(3-Ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 26.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of imidazo[1,2-a]pyridine-3-carboxylic acid (36.5 mg, 0.225 mmol) in dichloromethane (0.6 mL) was added N,N-dimethylformamide. Oxalyl chloride (84.5 μL, 0.169 mmol) was added and the mixture was stirred in a sealed vessel with ice cooling. The cooling was removed and the mixture was stirred for 3 hours with occasional venting to allow gases to escape. Diisopropylethylamine (21.6 μL, 0.124 mmol) and 3-ethyl-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amine (30 mg, 0.113 mmol) were added. The mixture was stirred for 30 minutes and then concentrated under reduced pressure. The material was purified using preparative thin layer chromatography, eluting with 10% methanol in dichloromethane containing 0.5% ammonium hydroxide solution. A second purification eluting with 5% methanol in ethyl acetate containing 0.5% ammonium hydroxide solution was carried out to provide N-(3-Ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (12.5 mg). MS (APCI), positive scan, m/z=411.3 (M+H).

Workup

  1. customThe cooling was removed
  2. stirringthe mixture was stirred for 3 hours with occasional venting
  3. stirringThe mixture was stirred for 30 minutes
  4. concentrationconcentrated under reduced pressure
  5. customThe material was purified
  6. washeluting with 10% methanol in dichloromethane containing 0.5% ammonium hydroxide solution
  7. customA second purification
  8. washeluting with 5% methanol in ethyl acetate containing 0.5% ammonium hydroxide solution

Sources & evidence

ORD record
ord-cae892800fc04d10b4ddef6f348c7bc5
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Linked notes

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