Formaldehyde → HCID 67260053, compound

HRID 79288Notes

Reaction equation

HRID 79288 reaction equation
[ClH:1].Cl.[CH2:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[NH:14][C:15]([C:17]2[N:21]3[CH:22]=[CH:23][C:24]([C:26]([N:28]4[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]4)=[O:27])=[CH:25][C:20]3=[N:19][CH:18]=2)=[O:16])[N:7]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([CH3:41])[N:36]=2)[N:6]=1)[CH3:4].[C:42](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C=O>ClCCl.CO>[ClH:1].[ClH:1].[CH2:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[NH:14][C:15]([C:17]2[N:21]3[CH:22]=[CH:23][C:24]([C:26]([N:28]4[CH2:29][CH2:30][N:31]([CH3:42])[CH2:32][CH2:33]4)=[O:27])=[CH:25][C:20]3=[N:19][CH:18]=2)=[O:16])[N:7]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([CH3:41])[N:36]=2)[N:6]=1)[CH3:4]

Participants

5

Reactant 3

HCID 712Formaldehyde2×HCID 5049666Sodium triacetoxyborohydride2×HCID 67259638N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(piperazine-1-carbonyl)imidazo[1,2-a]pyridine-3-carboxamide dihydrochloride

Product 1

HCID 67260053HCID 67260053, compound

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(piperazine-1-carbonyl)imidazo[1,2-a]pyridine-3-carboxamide dihydrochloride (Example 12; 5 mg, 0.0084 mmol) in dichloromethane/methanol (1:1; 1 mL) was added an excess of sodium triacetoxyborohydride and formaldehyde solution. The mixture was stirred at ambient temperature for 2 hours. Further excess sodium triacetoxyborohydride and formaldehyde solution were added and the mixture was stirred an additional 0.5 hours. The mixture was concentrated under a stream of nitrogen and the residue was purified using preparative thin layer chromatography on silica, eluting with 15% methanol and 0.5% ammonium hydroxide in dichloromethane to provide the desired product (free base form). This material was dissolved in methanol and filtered. To the filtrate was added hydrogen chloride (1 mL; 2M in ether) and the solvent was evaporated to a residual film under a stream of nitrogen. The material was dried under high vacuum to give N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(4-methylpiperazine-1-carbonyl)imidazo[1,2-a]pyridine-3-carboxamide dihydrochloride (3.3 mg). MS (APCI), positive scan, m/z=537.3 (M+H).

Workup

  1. stirringthe mixture was stirred an additional 0.5 hours
  2. concentrationThe mixture was concentrated under a stream of nitrogen
  3. customthe residue was purified
  4. washeluting with 15% methanol and 0.5% ammonium hydroxide in dichloromethane

Sources & evidence

ORD record
ord-3b8d991aad2542fe857ee856471b43a7
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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