Реакция #168357

Уравнение реакции

2-bromo-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile

(S)-2-(trifluoromethyl)pyrrolidine

potassium fluoride

N,N-diisopropylethylamine

→

4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(2S)-2-(trifluoromethyl)pyrrolidin-1-yl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile

Растворители

DMSO

ethyl acetate

Условия реакции

Обработка

1. 1
   ДругоеThe vial was sealed
2. 2
   ТемператураThe reaction mixture was cooled to room temperature
3. 3
   Промывкаwashed with water
4. 4
   СушкаThe organic layer was dried over sodium sulfate
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеconcentrated under reduced pressure
7. 7
   ДругоеThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

Методика

To a vial was added 2-bromo-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Preparative Example 3.1, 350 mg, 0.79 mmol), (S)-2-(trifluoromethyl)pyrrolidine (purchased from Sigma Aldrich) (219 mg, 1.57 mmol), potassium fluoride (229 mg, 3.93 mmol), DMSO (2.4 mL), and N,N-diisopropylethylamine (0.69 mL, 3.93 mmol). The vial was sealed and heated to 100° C. for 16 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and washed with water and then brine. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to afford 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(2S)-2-(trifluoromethyl)pyrrolidin-1-yl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C25H26ClF3N6 [M+H]+ 503. found 503.

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