3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amine → 7-(2-(dimethylamino)ethoxy)-N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 706607Notes

Reaction equation

HRID 706607 reaction equation
[CH3:1][C:2]1[C:10]2[C:9]([NH2:11])=[CH:8][CH:7]=[CH:6][C:5]=2[N:4]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[N:14]=2)[N:3]=1.[CH3:20][N:21]([CH3:39])[CH2:22][CH2:23][O:24][C:25]1[CH:30]=[CH:29][N:28]2[C:31]([C:34](OCC)=[O:35])=[CH:32][N:33]=[C:27]2[CH:26]=1>O1CCCCC1.O1CCCC1>[CH3:20][N:21]([CH3:39])[CH2:22][CH2:23][O:24][C:25]1[CH:30]=[CH:29][N:28]2[C:31]([C:34]([NH:11][C:9]3[CH:8]=[CH:7][CH:6]=[C:5]4[C:10]=3[C:2]([CH3:1])=[N:3][N:4]4[CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[N:14]=3)=[O:35])=[CH:32][N:33]=[C:27]2[CH:26]=1

Participants

5

Reactant 2

HCID 672609383-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amineHCID 67976325Ethyl 7-(2-(dimethylamino)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate

Product 1

HCID 573868987-(2-(dimethylamino)ethoxy)-N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 51.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8894TetrahydropyranSolvent

Procedure

3-Methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amine (59 mg, 0.24 mmol) was dissolved in tetrahydropyran (DriSolve; 1.2 mL) and degassed before back-filling with nitrogen. The solution was cooled in an ice water bath for 15 minutes before dropwise addition of lithium bis(trimethylsilyl)amide (0.25 mL, 1 M in tetrahydrofuran). The reaction stirred for 10 minutes before dropwise addition into a solution of ethyl 7-(2-(dimethylamino)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (31 mg, 0.12 mmol) in tetrahydrofuran (DriSolve; 1.2 mL) cooled in an ice-water bath. The reaction was then stirred while being cooled in the ice-water bath for 1.5 hours. The reaction was quenched with water and concentrated. Purification using reverse phase chromatography, eluting with a gradient from 10% to 60% ACN/water, gave 7-(2-(dimethylamino)ethoxy)-N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (30 mg). MS m/z 484.1 (M+1, APCI+).

Workup

  1. customdegassed before back-filling with nitrogen
  2. temperatureThe solution was cooled in an ice water bath for 15 minutes before dropwise addition of lithium bis(trimethylsilyl)amide (0.25 mL, 1 M in tetrahydrofuran)
  3. temperaturecooled in an ice-water bath
  4. customThe reaction was quenched with water
  5. concentrationconcentrated
  6. customPurification
  7. washeluting with a gradient from 10% to 60% ACN/water

Sources & evidence

ORD record
ord-23598aa0598c4596b557357a06d0d588
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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