Reaktion #356958

Reaktionsgleichung

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

Ausbeute 60.9%

Lösungsmittel

2-ethoxyethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling to room temperature
2. 2
   FiltrationThe resulting solid is collected by filtration
3. 3
   Waschenwashed with water
4. 4
   workup.DISSOLUTIONSome of the product dissolves in water
5. 5
   Sonstigewhich is recovered
6. 6
   Extraktionby extracting the aqueous layer with solution of 95:5 methylene chloride/methanol
7. 7
   SonstigeThe organic layer is evaporated
8. 8
   Sonstigeto provide crude product
9. 9
   SonstigeThe combined solids are purified by silica gel chromatography (gradient 95:5methylene chloride/methanol to 4:1 methylene chloride/methanol)

Vorschrift

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.

Quelle