Reaktion #1865241

Reaktionsgleichung

6-amino-4-((2-methoxyethyl)amino)nicotinonitrile

intermediate 75

6-amino-4-((2-methoxyethyl)amino)nicotinonitrile

(racemic) 1-(2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-3-methylpyrrolidin-2-one

intermediate 331

(racemic) 1-(2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-3-methylpyrrolidin-2-one

di(1H-1,2,4-triazol-1-yl)methanone

→

title compound

(racemic) N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-(3-methyl-2-oxopyrrolidin-1-yl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Lösungsmittel

DMF

DMF

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added
2. 2
   Temperaturto warm to room temperature
3. 3
   Sonstigequenched by the addition of MeOH
4. 4
   workup.ADDITIONThe reaction mixture was diluted with EtOAc, phases
5. 5
   Sonstigewere separated
6. 6
   Extraktionthe water phase was extracted with EtOAc
7. 7
   WaschenThe combined organic phases were washed with water and brine
8. 8
   Sonstigedried
9. 9
   Filtrationfiltered
10. 10
    Sonstigeevaporated
11. 11
    SonstigeThe crude product was purified by silica gel column chromatography
12. 12
    Wascheneluting with a gradient of MeOH (0-5%) in DCM
13. 13
    workup.ADDITIONFractions containing the product
14. 14
    Einengenconcentrated
15. 15
    Sonstigedried

Vorschrift

A solution of 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 81 mg, 0.422 mmol) in anhydrous DMF (0.5 ml) was added drop wise to a mixture of di(1H-1,2,4-triazol-1-yl)methanone (77 mg, 0.422 mmol) and DMF (0.5 ml) cooled at 0° C. After stirring for 2 h at 0° C. a solution of (racemic) 1-(2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-3-methylpyrrolidin-2-one (intermediate 331, 68 mg, 0.212 mmol) in DMF (0.5 ml) was added. The suspension was allowed to warm to room temperature, was continued to stir for 21 h and quenched by the addition of MeOH. The reaction mixture was diluted with EtOAc, phases were separated and the water phase was extracted with EtOAc. The combined organic phases were washed with water and brine, dried using Na2SO4, filtered and evaporated. The crude product was purified by silica gel column chromatography eluting with a gradient of MeOH (0-5%) in DCM. Fractions containing the product were combined, concentrated and dried to yield the title compound as a colorless residue. (UPLC-MS 3) tR 0.96 min, ESI-MS 524.4 [M+H]+.

Quelle