Reaction #166591

Reaction equation

N-(1-((6-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)pyridin-2-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

hydrogen chloride

→

N-(1-((6-(2,3-dihydroxypropoxy)pyridin-2-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide dihydrochloride

Yield 62.2%

Solvents

THF

Conditions

Workup

1. 1
   ConcentrationThe mixture was concentrated under a stream of nitrogen
2. 2
   workup.DISSOLUTIONthe residue was dissolved in a mixture of methanol and dichloromethane
3. 3
   workup.ADDITIONA solution of ammonium hydroxide was added
4. 4
   OtherThe material was purified
5. 5
   Washeluting with 10% methanol in dichloromethane containing 0.5% ammonium hydroxide
6. 6
   workup.DISSOLUTIONThe isolated product was dissolved in a mixture of methanol and dichloromethane
7. 7
   workup.ADDITIONtreated with concentrated hydrochloric acid (0.05 mL)
8. 8
   OtherThe solvent was removed under reduced pressure

Procedure

To a solution of N-(1-((6-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)pyridin-2-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (12 mg, 0.023 mmol) in THF (1 mL) was added hydrogen chloride (0.5 mL, 2.0 mmol; 4M solution in 1,4-dioxane). The mixture was stirred at ambient temperature for 3 hours. The mixture was concentrated under a stream of nitrogen and the residue was dissolved in a mixture of methanol and dichloromethane. A solution of ammonium hydroxide was added to neutralize. The material was purified using preparative thin layer chromatography, eluting with 10% methanol in dichloromethane containing 0.5% ammonium hydroxide. The isolated product was dissolved in a mixture of methanol and dichloromethane and treated with concentrated hydrochloric acid (0.05 mL). The solvent was removed under reduced pressure to give N-(1-((6-(2,3-dihydroxypropoxy)pyridin-2-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide dihydrochloride (8 mg). MS (APCI), positive scan, m/z=487.2 (M+H).

Source