Trimethylsilyl cyanide → 4-(8-(3,4-Difluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)-1-(6-methylpyrimidin-4-yl)piperidine-4-carbonitrile

HRID 451537Notes

Reaction equation

HRID 451537 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]2)[CH:3]=1.[F:15][C:16]1[CH:17]=[C:18]([C:23]2[C:24]3[N:25]([N:29]=[C:30]([NH2:32])[N:31]=3)[CH:26]=[CH:27][CH:28]=2)[CH:19]=[CH:20][C:21]=1[F:22].C[Si]([C:37]#[N:38])(C)C>CC(O)=O>[F:15][C:16]1[CH:17]=[C:18]([C:23]2[C:24]3[N:25]([N:29]=[C:30]([NH:32][C:11]4([C:37]#[N:38])[CH2:12][CH2:13][N:8]([C:4]5[CH:3]=[C:2]([CH3:1])[N:7]=[CH:6][N:5]=5)[CH2:9][CH2:10]4)[N:31]=3)[CH:26]=[CH:27][CH:28]=2)[CH:19]=[CH:20][C:21]=1[F:22]

Participants

5

Reactant 3

HCID 82115Trimethylsilyl cyanideHCID 61226887HCID 61226887, compoundHCID 673372048-(3,4-Difluorophenyl)-[1,2,4]triazolo[1,5-A]pyridin-2-amine

Product 1

HCID 583979704-(8-(3,4-Difluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)-1-(6-methylpyrimidin-4-yl)piperidine-4-carbonitrileYield 9%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of 1-(6-methylpyrimidin-4-yl)piperidin-4-one (see example 93b, 100 mg, 0.523 mmol) and 8-(3,4-difluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine (129 mg, 0.523 mmol) in AcOH was added dropwise trimethylsilyl cyanide (196 μL, 1.57 mmol) and the resulting mixture stirred at room temperature for 88 hours. The mixture was then poured onto NaOH (6 M, 6 mL) and stirred for 10 minutes. The precipitate was then filtered off and dried. Purification by chromatography (silica gel, 20 g, 30 to 100% ethyl acetate in heptane) afforded the title compound (20 mg, 9%) as a yellow solid. MS ISP (m/e): 447.4 [(M+H)+].

Workup

  1. additionThe mixture was then poured onto NaOH (6 M, 6 mL)
  2. stirringstirred for 10 minutes
  3. filtrationThe precipitate was then filtered off
  4. customdried
  5. customPurification by chromatography (silica gel, 20 g, 30 to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-a89d565b9d8c4b6299e58c537adc5465
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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