Reaktion #1865227

Reaktionsgleichung

LHMDS

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

intermediate 311

phenyl 7-(dimethoxymethyl)-6-(tetrahydro-2H-pyran-4-yl)-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

NH4Cl

→

title compound

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

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added
2. 2
   Temperaturthe mixture warmed to room temperature
3. 3
   Extraktionextracted with EtOAc
4. 4
   WaschenThe organic layer was washed with brine
5. 5
   Trocknendried over MgSO4
6. 6
   Sonstigeevaporated
7. 7
   SonstigeThe residue was then purified by normal phase chromatography
8. 8
   Wascheneluting with a gradient from hexane to 50% EtOAc in hexane
9. 9
   workup.ADDITIONProduct containing fractions
10. 10
    Sonstigeevaporated

Vorschrift

A solution of LHMDS in THF (0.9 M, 2.32 ml, 2.09 mmol) was added to phenyl 7-(dimethoxymethyl)-6-(tetrahydro-2H-pyran-4-yl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (intermediate 311, 700 mg, 0.95 mmol) and 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 183 mg, 0.95 mmol) in THF (10 ml) cooled at −78° C. with a dry ice/acetone bath. After stirring for 2 h at −78° C. aqueous NH4Cl was added, the mixture warmed to room temperature and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4 and evaporated. The residue was then purified by normal phase chromatography using a 24 g RediSep® column, eluting with a gradient from hexane to 50% EtOAc in hexane. Product containing fractions were then combined and evaporated to give the title compound as a white solid. (UPLC-MS 3) tR 1.07 min; ESI-MS 511.4 [M+H]+.

Quelle