Реакция #356958

Уравнение реакции

4-chloro-6-nitro-7-(4-pyrrolidin-1-ylpiperidin-1-yl)quinoline-3-carbonitrile

3-chloro-4-[(1-methyl-1H-imidazole-2-yl)sulfanyl]aniline

pyridine hydrochloride

sodium bicarbonate

→

4-({3-chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-6-nitro-7-(4-pyrrolidin-1-ylpiperidin-1-yl)quinoline-3-carbonitrile

Выход 60.9%

Растворители

2-ethoxyethanol

Условия реакции

Обработка

1. 1
   ТемператураAfter cooling to room temperature
2. 2
   ФильтрацияThe resulting solid is collected by filtration
3. 3
   Промывкаwashed with water
4. 4
   workup.DISSOLUTIONSome of the product dissolves in water
5. 5
   Другоеwhich is recovered
6. 6
   Экстракцияby extracting the aqueous layer with solution of 95:5 methylene chloride/methanol
7. 7
   ДругоеThe organic layer is evaporated
8. 8
   Другоеto provide crude product
9. 9
   ДругоеThe combined solids are purified by silica gel chromatography (gradient 95:5methylene chloride/methanol to 4:1 methylene chloride/methanol)

Методика

A mixture of 0.5 g (1.45 mmol) of 4-chloro-6-nitro-7-(4-pyrrolidin-1-ylpiperidin-1-yl)quinoline-3-carbonitrile, 0.38 g (1.6 mmol) of 3-chloro-4-[(1-methyl-1H-imidazole-2-yl)sulfanyl]aniline and 0.17 g of pyridine hydrochloride in 7.0 mL of 2-ethoxyethanol is heated at 105° C. for 1 hour. After cooling to room temperature, the mixture is stirred with 15 mL of saturated solution of sodium bicarbonate. The resulting solid is collected by filtration and washed with water. Some of the product dissolves in water, which is recovered by extracting the aqueous layer with solution of 95:5 methylene chloride/methanol. The organic layer is evaporated to provide crude product. The combined solids are purified by silica gel chromatography (gradient 95:5methylene chloride/methanol to 4:1 methylene chloride/methanol) gives 0.52 g of 4-({3-chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-6-nitro-7-(4-pyrrolidin-1-ylpiperidin-1-yl)quinoline-3-carbonitrile as an orange solid, mp 220-230° C.

Источник