4-(8-(3,4-Difluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)-1-(6-methylpyrimidin-4-yl)piperidine-4-carbonitrile → 8-(3,4-Difluorophenyl)-N-(4-methyl-1-(6-methylpyrimidin-4-yl)piperidin-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine

HRID 451542Notes

Reaction equation

HRID 451542 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[C:10]3[N:11]([N:15]=[C:16]([NH:18][C:19]4([C:32]#N)[CH2:24][CH2:23][N:22]([C:25]5[CH:30]=[C:29]([CH3:31])[N:28]=[CH:27][N:26]=5)[CH2:21][CH2:20]4)[N:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:6][C:7]=1[F:8].C[Mg]Br>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[C:10]3[N:11]([N:15]=[C:16]([NH:18][C:19]4([CH3:32])[CH2:24][CH2:23][N:22]([C:25]5[CH:30]=[C:29]([CH3:31])[N:28]=[CH:27][N:26]=5)[CH2:21][CH2:20]4)[N:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

4

Reactant 2

HCID 583979704-(8-(3,4-Difluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)-1-(6-methylpyrimidin-4-yl)piperidine-4-carbonitrileHCID 178418573HCID 178418573, compound

Product 1

HCID 583980568-(3,4-Difluorophenyl)-N-(4-methyl-1-(6-methylpyrimidin-4-yl)piperidin-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-amineYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(8-(3,4-difluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)-1-(6-methylpyrimidin-4-yl)piperidine-4-carbonitrile (Example 231) (50 mg, 112 μmol) in THF (2 mL) was added methylmagnesium bromide (1.4 M in toluene:THF, 240 μL, 336 μmol) dropwise at 0° C., and the resulting mixture was allowed to warm up to room temperature and stirred for 3 hours. Then the mixture was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layers were washed with brine, dried over sodium sulfate, filtered and evaporated. Purification by chromatography (silica gel, 10 g, 0 to 10% methanol in dichloromethane) afforded the title compound (9 mg, 19%) as a light yellow solid.

Workup

  1. customThen the mixture was quenched with saturated aqueous ammonium chloride solution
  2. extractionextracted with ethyl acetate
  3. washThe organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by chromatography (silica gel, 10 g, 0 to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-b235718d215c48ebbea6efc2dbe66130
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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