반응 #820869

반응 방정식

morpholine

1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride

1-hydroxybenzotriazole hydrate

N,N-diisopropylethylamine

HCl

sodium bicarbonate

→

title compound

1-[4-(3-Chloro-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridin-7-yl]-1-morpholin-4-yl-methanone hydrochloride

용매

dimethylformamide

ethyl acetate

DCM

반응 조건

후처리

1. 1
   기타The layers were separated
2. 2
   세척the organic layer washed with water 3 times, brine
3. 3
   건조dried (MgSO4)
4. 4
   기타evaporated
5. 5
   기타to give a gum
6. 6
   기타Purified on MDAP
7. 7
   기타the product split into two fractions
8. 8
   기타The first fraction was evaporated
9. 9
   workup.DISSOLUTIONdissolved in ethyl acetate
10. 10
    세척washed as above,
11. 11
    기타dried
12. 12
    기타evaporate
13. 13
    기타to give a solid
14. 14
    기타This was triturated with ether
15. 15
    기타purified by MDAP and chromatography on silica gel
16. 16
    세척eluting with dichloromethane/methanol, 20:1
17. 17
    기타to give the free base which
18. 18
    기타evaporated
19. 19
    기타triturated with ether

실험 절차

A mixture of 4-(3-chloro-phenylamino)-1H-methyl-1H-pyrrolo[3,2-c]pyridin-7-carboxylic acid (29 mg), morpholine (36 ul), 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (76 mg), 1-hydroxybenzotriazole hydrate (54 mg) and N,N-diisopropylethylamine (140 ul) in dimethylformamide (2 ml) was stirred overnight then added to a mixture of ethyl acetate (20 ml) water (20 ml) and saturated sodium bicarbonate (10 ml). The layers were separated and the organic layer washed with water 3 times, brine, dried (MgSO4) and evaporated to give a gum. Purified on MDAP and the product split into two fractions. The first fraction was evaporated, dissolved in ethyl acetate and washed as above, dried and evaporate to give a solid. This was triturated with ether and purified by MDAP and chromatography on silica gel, eluting with dichloromethane/methanol, 20:1, to give the free base which was taken up in DCM treated with ethereal HCl, evaporated and triturated with ether to give the title compound as a solid (11 mg)

출처