Reaktion #1865186

Reaktionsgleichung

N-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-N-(2-(dimethylamino)ethyl)methanesulfonamide

intermediate 201

N-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-N-(2-(dimethylamino)ethyl)methanesulfonamide

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

intermediate 75

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

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

→

title compound

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

Lösungsmittel

DMF

DMF

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto warm to room temperature
2. 2
   workup.STIRRINGThe reaction mixture was stirred for 14 h at room temperature
3. 3
   Sonstigequenched by the addition of MeOH
4. 4
   Einengenconcentrated
5. 5
   workup.ADDITIONThe residue was diluted with EtOAc and water
6. 6
   Filtrationfiltered
7. 7
   Sonstigeto remove insoluble byproducts
8. 8
   SonstigePhases were separated
9. 9
   Waschenthe aqueous layer was washed with EtOAc
10. 10
    Waschenwashed with water
11. 11
    Sonstigedried
12. 12
    Filtrationfiltered
13. 13
    Sonstigeevaporated
14. 14
    SonstigeThe crude product was purified
15. 15
    Wascheneluting with a gradient of MeOH (0-5%) in DCM
16. 16
    workup.ADDITIONFractions containing the product
17. 17
    Sonstigeevaporated

Vorschrift

A solution of 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 720 mg, 3.75 mmol) in anhydrous DMF (6 ml) was added dropwise to a mixture of di(1H-1,2,4-triazol-1-yl)methanone (660 mg, 3.62 mmol) and DMF (6 ml) cooled at 0° C. After stirring for 50 minutes at 0° C. the reaction mixture was allowed to warm to room temperature and a solution of N-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-N-(2-(dimethylamino)ethyl)methanesulfonamide (intermediate 201, 697 mg, 1.803 mmol) in DMF (6 ml) was added. The reaction mixture was stirred for 14 h at room temperature, quenched by the addition of MeOH and concentrated. The residue was diluted with EtOAc and water, filtered to remove insoluble byproducts. Phases were separated and the aqueous layer was washed with EtOAc. The organic layers were combined, washed with water, dried using Na2SO4, filtered and evaporated. The crude product was purified using silica gel column chromatography eluting with a gradient of MeOH (0-5%) in DCM. Fractions containing the product were combined and evaporated to yield the title compound as an orange resin. (UPLC-MS 3) tR 0.81 min, ESI-MS 605.3 [M+H]+.

Quelle