Dichloromethane → N-(3-ethyl-1-((1-(2-(piperazin-1-yl)ethyl)-1H-pyrazol-3-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide trihydrochloride

HRID 79279Notes

Reaction equation

HRID 79279 reaction equation
[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][C:13]([C:15]2[N:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]3=[N:17][CH:16]=2)=[O:14])[N:5]([CH2:24][C:25]2[CH:29]=[CH:28][N:27]([CH2:30][CH2:31][N:32]3[CH2:37][CH2:36][N:35](C(OC(C)(C)C)=O)[CH2:34][CH2:33]3)[N:26]=2)[N:4]=1)[CH3:2].FC(F)(F)C(O)=O.[Cl:52]CCl>>[ClH:52].[ClH:52].[ClH:52].[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][C:13]([C:15]2[N:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]3=[N:17][CH:16]=2)=[O:14])[N:5]([CH2:24][C:25]2[CH:29]=[CH:28][N:27]([CH2:30][CH2:31][N:32]3[CH2:33][CH2:34][NH:35][CH2:36][CH2:37]3)[N:26]=2)[N:4]=1)[CH3:2]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 67261385tert-butyl 4-(2-(3-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)-1H-pyrazol-1-yl)ethyl)piperazine-1-carboxylate

Product 1

HCID 86672208N-(3-ethyl-1-((1-(2-(piperazin-1-yl)ethyl)-1H-pyrazol-3-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide trihydrochloride

Procedure

To a solution of tert-butyl 4-(2-(3-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)-1H-pyrazol-1-yl)ethyl)piperazine-1-carboxylate (21.5 mg; 0.0360 mmol) in dichloromethane (1 mL) was added trifluoroacetic acid (1 mL). The mixture was stirred for 1 hour. The solvent was removed under reduced pressure and the residue was dissolved in a mixture of methanol and dichloromethane. Ammonium hydroxide solution was added to neutralize. The material was purified by preparative thin layer chromatography on silica, eluting with 15% methanol in dichloromethane containing 0.5% ammonium hydroxide solution. The isolated product was dissolved in a mixture of methanol and ethyl acetate and treated with hydrogen chloride (1 mL; 2M in ether). Removal of solvent under reduced pressure followed by high vacuum gave N-(3-ethyl-1-((1-(2-(piperazin-1-yl)ethyl)-1H-pyrazol-3-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide trihydrochloride (9.5 mg). MS (APCI), positive scan, m/z=498.3 (M+H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in a mixture of methanol and dichloromethane
  3. additionAmmonium hydroxide solution was added
  4. customThe material was purified by preparative thin layer chromatography on silica
  5. washeluting with 15% methanol in dichloromethane containing 0.5% ammonium hydroxide solution
  6. dissolutionThe isolated product was dissolved in a mixture of methanol and ethyl acetate
  7. additiontreated with hydrogen chloride (1 mL; 2M in ether)
  8. customRemoval of solvent under reduced pressure

Sources & evidence

ORD record
ord-900730ae6576417e82f3ed1b7612a7e2
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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