1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-(6-Acetoxy-7,8-dihydro-6H-pyrrolo[2',1':2,3]imidazo[4,5-b]pyridin-3-yl)-5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxamide

Temperatur

20 °C

A solution of 0.25 g (0.87 mmol) of 5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acid, prepared in step 1.1, 0.166 g (0.87 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide and 0.117 g (0.87 mmol) of N-1-hydroxybenzotriazole in 3 ml of dimethylformamide is stirred at 20° C. for 15 minutes. The reaction mixture is subsequently admixed with 0.245 g (1.04 mmol) of 6-acetoxy-7,8-dihydro-6H-pyrrolo[2′,1′:2,3]imidazo[4,5-b]pyridin-3-amine (compound IV-b), in solution in 3 ml of dimethylformamide. The reaction mixture is subsequently stirred at 20° C. for 16 hours and then concentrated under reduced pressure, poured into 50 ml of water and extracted with three times 50 ml of ethyl acetate. The organic phases are combined, then washed with twice 20 ml of saturated sodium hydrogen carbonate solution, once with 20 ml of water and then once with 50 ml of saturated sodium chloride solution, dried over sodium sulfate and then concentrated under reduced pressure. The product obtained is purified by chromatography on a silica column, eluting with a mixture of dichloromethane and methanol. The product thus purified is finally triturated in hot diisopropyl ether and filtered while hot to give 0.27 g of the expected product.

1. stirringThe reaction mixture is subsequently stirred at 20° C. for 16 hours
2. concentrationconcentrated under reduced pressure
3. additionpoured into 50 ml of water
4. extractionextracted with three times 50 ml of ethyl acetate
5. washwashed with twice 20 ml of saturated sodium hydrogen carbonate solution, once with 20 ml of water
6. dry with materialonce with 50 ml of saturated sodium chloride solution, dried over sodium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe product obtained
9. customis purified by chromatography on a silica column
10. washeluting with a mixture of dichloromethane and methanol
11. customThe product thus purified
12. customis finally triturated in hot diisopropyl ether
13. filtrationfiltered while hot

ORD-Eintrag

ord-b5912a65fb914b2c99030e2202a27424

Quelldatensatz

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08153796B2