反応 #44970

反応方程式

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

収率 61.6%

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

収率 61.6%

溶媒

chloroform

反応条件

後処理

1. 1
   温度cooling
2. 2
   温度cooling for 10 minutes
3. 3
   その他To the resulting reaction solution
4. 4
   その他obtained in Reference Example 79
5. 5
   workup.STIRRINGthe mixture is stirred at room temperature for 2 hours and at 50° C.
6. 6
   温度under heating for 5 hours
7. 7
   温度cooling
8. 8
   workup.STIRRINGthe mixture is stirred at room temperature for 0.5 hours
9. 9
   抽出extracted with chloroform
10. 10
    洗浄The organic layer is washed with saturated brine
11. 11
    乾燥dried over sodium sulfate
12. 12
    その他the solvent is evaporated under reduced pressure
13. 13
    その他The residue is purified by NH-silica gel column chromatography (eluent: ethyl acetate followed by ethyl acetate/methanol=10/1)
14. 14
    ろ過collected by filtration

実験手順

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).

出典