Реакция #168430

Уравнение реакции

7-chloro-4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile

CsF

dimethylamine

DMSO

→

4-(5-chloropyridin-3-yl)-7-(dimethylamino)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile

Растворители

EtOAc

THF

Условия реакции

Обработка

1. 1
   ДругоеThe vial was sealed
2. 2
   ТемператураThe reaction was cooled to room temperature
3. 3
   Промывкаwashed with water (5 mL) and brine (5 mL)
4. 4
   СушкаThe organic layer was dried over Na2SO4
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеconcentrated
7. 7
   ДругоеThe residue was purified on a silica gel column with 0 to 100% EtOAc/hexanes

Методика

A dry vial, under an atmosphere of nitrogen, was charged with 7-chloro-4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Example 11.2, step 1; 50 mg, 0.095 mmol), CsF (101 mg, 0.666 mmol), dimethylamine (0.476 mL of a 2M solution in THF, 0.952 mmol) and DMSO (1 mL). The vial was sealed and heated to 100° C. for 8 hours. The reaction was cooled to room temperature, diluted with EtOAc (25 mL) and washed with water (5 mL) and brine (5 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified on a silica gel column with 0 to 100% EtOAc/hexanes to afford 4-(5-chloropyridin-3-yl)-7-(dimethylamino)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd for C29H36ClN7O [M+H]+=534. found=534.

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