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

HRID 79409Notes

Reaction equation

HRID 79409 reaction equation
CC1(C)[O:6][CH:5]([CH2:7][O:8][C:9]2[N:14]=[C:13]([CH2:15][N:16]3[C:24]4[C:19](=[C:20]([NH:25][C:26]([C:28]5[N:32]6[CH:33]=[CH:34][CH:35]=[CH:36][C:31]6=[N:30][CH:29]=5)=[O:27])[CH:21]=[CH:22][CH:23]=4)[C:18]([CH2:37][CH3:38])=[N:17]3)[CH:12]=[CH:11][CH:10]=2)[CH2:4][O:3]1.[ClH:40]>C1COCC1>[ClH:40].[ClH:40].[OH:6][CH:5]([CH2:4][OH:3])[CH2:7][O:8][C:9]1[N:14]=[C:13]([CH2:15][N:16]2[C:24]3[C:19](=[C:20]([NH:25][C:26]([C:28]4[N:32]5[CH:33]=[CH:34][CH:35]=[CH:36][C:31]5=[N:30][CH:29]=4)=[O:27])[CH:21]=[CH:22][CH:23]=3)[C:18]([CH2:37][CH3:38])=[N:17]2)[CH:12]=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67259775N-(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

Product 1

HCID 67260905N-(1-((6-(2,3-dihydroxypropoxy)pyridin-2-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide dihydrochlorideYield 62.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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).

Workup

  1. concentrationThe mixture was concentrated under a stream of nitrogen
  2. dissolutionthe residue was dissolved in a mixture of methanol and dichloromethane
  3. additionA solution of ammonium hydroxide was added
  4. customThe material was purified
  5. washeluting with 10% methanol in dichloromethane containing 0.5% ammonium hydroxide
  6. dissolutionThe isolated product was dissolved in a mixture of methanol and dichloromethane
  7. additiontreated with concentrated hydrochloric acid (0.05 mL)
  8. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-c22f2af3102c4334b84eed138b28f326
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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