Thionyl Chloride → N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 706608Notes

Reaction equation

HRID 706608 reaction equation
[N:1]1[CH:2]=[C:3]([C:10]([OH:12])=O)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.S(Cl)(Cl)=O.[CH3:17][C:18]1[C:26]2[C:25]([NH2:27])=[CH:24][CH:23]=[CH:22][C:21]=2[N:20]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[N:30]=2)[N:19]=1>>[CH3:17][C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][C:25]=2[NH:27][C:10]([C:3]2[N:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]3=[N:1][CH:2]=2)=[O:12])[N:20]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[N:30]=2)[N:19]=1

Participants

4

Reactant 3

HCID 24386Thionyl ChlorideHCID 73142Imidazo(1,2-a)pyridine-3-carboxylic acidHCID 672609383-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amine

Product 1

HCID 57386899N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 31.9%

Procedure

Imidazo[1,2-a]pyridine-3-carboxylic acid (62 mg, 0.38 mmol) was dissolved neat in thionyl chloride (112 mL, 1.5 mmol). The reaction mixture was stirred at ambient temperature for 1 hour before concentrating and drying under high vacuum for 16 hours. The resulting solid was dissolved in tetrahydrofuran (2 mL). 3-Methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amine (97 mg, 0.38 mmol) was added and the reaction was stirred at 70° C. in a sand bath for 6 hours. The mixture was concentrated and partitioned between ethyl acetate and saturated sodium bicarbonate. The ethyl acetate layer was washed with water and brine before drying over sodium sulfate and concentrating. Preparative Thin Layer Chromatography (Silica, 1 mm) of the crude material, eluting with 10% MeOH/DCM, gave N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (48 mg) in a band with Rf=0.6. MS m/z 397.3 (M+1, APCI+).

Workup

  1. concentrationbefore concentrating
  2. customdrying under high vacuum for 16 hours
  3. dissolutionThe resulting solid was dissolved in tetrahydrofuran (2 mL)
  4. stirringthe reaction was stirred at 70° C. in a sand bath for 6 hours
  5. concentrationThe mixture was concentrated
  6. custompartitioned between ethyl acetate and saturated sodium bicarbonate
  7. washThe ethyl acetate layer was washed with water and brine
  8. dry with materialbefore drying over sodium sulfate
  9. concentrationconcentrating
  10. washPreparative Thin Layer Chromatography (Silica, 1 mm) of the crude material, eluting with 10% MeOH/DCM

Sources & evidence

ORD record
ord-aab5cb1252a94352b248efd05f8eaa20
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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