تفاعل #168396

معادلة التفاعل

(R)-tert-butyl 3-methylpiperazine-1-carboxylate

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

potassium fluoride

DIEA

→

(R)-tert-butyl 4-(4-(5-chloropyridin-3-yl)-6-cyano-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridin-2-yl)-3-methylpiperazine-1-carboxylate

المذيبات

DMSO

EtOAc

ظروف التفاعل

المعالجة

1. 1
   أخرىThe reaction vial was capped
2. 2
   درجة الحرارةThe mixture was cooled to room temperature
3. 3
   غسيلThe mixture was washed with water and brine
4. 4
   تجفيفdried over sodium sulfate
5. 5
   ترشيحfiltered
6. 6
   تركيزconcentrated
7. 7
   أخرىThe residue was purified by column chromatography on silica gel
8. 8
   غسيلeluting with EtOAc/isohexane

الإجراء التجريبي

To a microwave vial was added (R)-tert-butyl 3-methylpiperazine-1-carboxylate (purchased from Astatech) (180 mg, 0.899 mmol), 2-bromo-4-(5-chloropyridin-3-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (200 mg, 0.450 mmol, Preparative Example 3.1), potassium fluoride (78 mg, 1.349 mmol), DMSO (1 ml) and DIEA (0.236 ml, 1.349 mmol). The reaction vial was capped and heated to 100° C. overnight. The mixture was cooled to room temperature and diluted with EtOAc. The mixture was washed with water and brine, then dried over sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel, eluting with EtOAc/isohexane to give (R)-tert-butyl 4-(4-(5-chloropyridin-3-yl)-6-cyano-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridin-2-yl)-3-methylpiperazine-1-carboxylate. MS ESI calc'd. for C30H38ClN7O2 [M+H]+ 564. found 564.

المصدر