Reaktion #1865231

Reaktionsgleichung

LHMDS

phenyl 6-bromo-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

intermediate 11

phenyl 6-bromo-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

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

intermediate 75

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

→

title compound

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

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirred for 5 min
2. 2
   Temperaturcooled to −70° C.
3. 3
   workup.STIRRINGwhile stirring for 30 min
4. 4
   Temperaturto warm to −15° C.
5. 5
   workup.STIRRINGstirred for 10 min
6. 6
   Temperaturcooled to −70° C.
7. 7
   Sonstigequenched with saturated aqueous NH4Cl
8. 8
   workup.ADDITIONThe reaction mixture was diluted with water and ethyl acetate, layers
9. 9
   Sonstigewere separated
10. 10
    Extraktionthe aqueous layer was extracted with ethyl acetate
11. 11
    WaschenThe combined organic layers were washed with water
12. 12
    Sonstigedried
13. 13
    Filtrationfiltered
14. 14
    Sonstigeevaporated
15. 15
    SonstigeThe crude product was purified by silica gel column chromatography
16. 16
    Wascheneluting with a gradient ethyl acetate (90-100%) in heptane
17. 17
    Sonstigeevaporated
18. 18
    Sonstigedried

Vorschrift

LHMDS (1M in THF, 0.36 mL, 0.360 mmol) was added to a solution of phenyl 6-bromo-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (intermediate 11, 148 mg, 0.345 mmol) and 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 70 mg, 0.346 mmol) in THF (3 ml) at −70° C. and stirred for 35 min. The reaction mixture was allowed to warm to −25° C., stirred for 5 min and cooled to −70° C. while stirring for 30 min. The reaction mixture was allowed to warm to −15° C., stirred for 10 min, cooled to −70° C. and quenched with saturated aqueous NH4Cl. The reaction mixture was diluted with water and ethyl acetate, layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water, dried using Na2SO4, filtered and evaporated. The crude product was purified by silica gel column chromatography eluting with a gradient ethyl acetate (90-100%) in heptane. Product fractions were combined, evaporated and dried to yield the title compound as a yellow solid. (UPLC-MS 3) tR 1.16 min, ESI-MS 505.1 [M+H]+. 1H NMR (600 MHz, CDCl3) δ 8.23 (s, 1H), 7.65 (s, 1H), 7.57 (s, 1H), 5.68 (s, 1H), 5.26-5.21 (m, 1H), 4.06-4.00 (m, 2H), 3.62 (t, 2H), 3.51-3.44 (m, 8H), 3.40 (s, 3H), 2.84 (t, 2H), 2.03-1.96 (m, 2H).

Quelle