Imidazo(1,2-a)pyridine-3-carboxylic acid → N-(3-ethyl-1-((2-methoxy-6-methylpyridin-3-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79366

Reaction equation

HRID 79366 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)Cl.S(Cl)(Cl)=O.[CH2:20]([C:22]1[C:30]2[C:29]([NH2:31])=[CH:28][CH:27]=[CH:26][C:25]=2[N:24]([CH2:32][C:33]2[C:34]([O:40][CH3:41])=[N:35][C:36]([CH3:39])=[CH:37][CH:38]=2)[N:23]=1)[CH3:21]>C1COCC1.ClCCCl>[CH2:20]([C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][C:29]=2[NH:31][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:24]([CH2:32][C:33]2[C:34]([O:40][CH3:41])=[N:35][C:36]([CH3:39])=[CH:37][CH:38]=2)[N:23]=1)[CH3:21]

Participants

5

Reactant 3

HCID 73142Imidazo(1,2-a)pyridine-3-carboxylic acidHCID 21879677DCM thionyl chlorideHCID 672595973-ethyl-1-((2-methoxy-6-methylpyridin-3-yl)methyl)-1H-indazol-4-amine

Product 1

HCID 67259571N-(3-ethyl-1-((2-methoxy-6-methylpyridin-3-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 35.9%

Reagents, catalysts & solvents 1

HCID 21493386Dce thfSolvent

Procedure

To imidazo[1,2-a]pyridine-3-carboxylic acid (118 mg, 0.729 mmol) was added a mixture of 3:1 DCM/thionyl chloride (4 mL). The mixture was stirred at ambient temperature for 3 hours and then concentrated to a residue under N2 stream. The residue was dried under high vacuum for 30 minutes. 3-Ethyl-1-((2-methoxy-6-methylpyridin-3-yl)methyl)-1H-indazol-4-amine (108 mg, 0.364 mmol) in THF/DCE (1:1; 8 mL) was added to the dry acid-chloride residue. The reaction mixture was heated at 75° C. for 30 minutes. The mixture was concentrated under reduced pressure and diluted with DCM. The solution was washed with saturated NaHCO3 aqueous solution, dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 5% MeOH 0.5% NH4OH in DCM to give the product (57.6 mg).

Workup

  1. concentrationconcentrated to a residue under N2 stream
  2. customThe residue was dried under high vacuum for 30 minutes
  3. temperatureThe reaction mixture was heated at 75° C. for 30 minutes
  4. concentrationThe mixture was concentrated under reduced pressure
  5. additiondiluted with DCM
  6. washThe solution was washed with saturated NaHCO3 aqueous solution
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with 5% MeOH 0.5% NH4OH in DCM

Sources & evidence

ORD record
ord-883da2428cfc48a3ba661eab93affe6c
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Linked notes

Loading…