Reaktion #44970

Reaktionsgleichung

hydrochloric acid

2-Amino-5-methylpyridine

trimethyl aluminum hexane

sodium hydrogen carbonate

methyl 3-({[trans-4-(3-oxomorpholin-4-yl)cyclohexyl]carbonyl}amino)furo[3,2-b]pyridine-2-carboxylate

→

title compound

Ausbeute 61.6%

N-(5-methylpyridine-2-yl)-3-({[trans-4-(3-oxomorpholin-4-yl)cyclohexyl]carbonyl}amino)furo[3,2-b]pyridine-2-carboxamide

Ausbeute 61.6%

Lösungsmittel

chloroform

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturcooling
2. 2
   Temperaturcooling for 10 minutes
3. 3
   SonstigeTo the resulting reaction solution
4. 4
   Sonstigeobtained in Reference Example 79
5. 5
   workup.STIRRINGthe mixture is stirred at room temperature for 2 hours and at 50° C.
6. 6
   Temperaturunder heating for 5 hours
7. 7
   Temperaturcooling
8. 8
   workup.STIRRINGthe mixture is stirred at room temperature for 0.5 hours
9. 9
   Extraktionextracted with chloroform
10. 10
    WaschenThe organic layer is washed with saturated brine
11. 11
    Trocknendried over sodium sulfate
12. 12
    Sonstigethe solvent is evaporated under reduced pressure
13. 13
    SonstigeThe residue is purified by NH-silica gel column chromatography (eluent: ethyl acetate followed by ethyl acetate/methanol=10/1)
14. 14
    Filtrationcollected by filtration

Vorschrift

2-Amino-5-methylpyridine (81 mg) is dissolved in chloroform (5 ml). After adding 0.98 M trimethyl aluminum-hexane solution (763 μl) under ice-cooling, the reaction solution is stirred under ice-cooling for 10 minutes, and then at room temperature for 0.5 hours. To the resulting reaction solution is added methyl 3-({[trans-4-(3-oxomorpholin-4-yl)cyclohexyl]carbonyl}amino)furo[3,2-b]pyridine-2-carboxylate (150 mg) obtained in Reference Example 79, and the mixture is stirred at room temperature for 2 hours and at 50° C. under heating for 5 hours. To the reaction solution is added 10% hydrochloric acid (3 ml) under ice-cooling, and the mixture is stirred at room temperature for 0.5 hours. The reaction solution is then neutralized by adding saturated aqueous sodium hydrogen carbonate solution, and extracted with chloroform. The organic layer is washed with saturated brine, dried over sodium sulfate, and the solvent is evaporated under reduced pressure. The residue is purified by NH-silica gel column chromatography (eluent: ethyl acetate followed by ethyl acetate/methanol=10/1). The resulting solid is suspended in diethyl ether, and collected by filtration to give the title compound (110 mg).

Quelle