反応 #214456

反応方程式

4-amino-2-chloro-6,7-dimethoxyquinazoline

8-(4-piperidinyl)-8-azaspiro[4,5]decan-7,9-dione

sodium carbonate

→

8-[1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-piperidinyl]-8-azaspiro[4,5]decan-7,9-dione hydrochloride

溶媒

dimethylformamide

反応条件

後処理

1. 1
   ろ過filtered
2. 2
   その他the filtrate evaporated
3. 3
   workup.ADDITIONThe residue is poured
4. 4
   workup.STIRRINGwith stirring
5. 5
   温度cooling into 300 ml of water
6. 6
   workup.ADDITIONthe mixture diluted with 1400 ml of water
7. 7
   ろ過filtered
8. 8
   その他The solids are triturated with 1600 ml of ethyl acetate and 10 ml of saturated aqueous sodium carbonate
9. 9
   その他The organic layer is separated
10. 10
    その他dried
11. 11
    その他evaporated
12. 12
    workup.DISSOLUTIONthe residue dissolved in 1,000 ml of ethyl acetate
13. 13
    ろ過the precipitate filtered off
14. 14
    その他recrystallized from aqueous methanol

実験手順

The mixture of 70 g of 4-amino-2-chloro-6,7-dimethoxyquinazoline, 73.2 g of 8-(4-piperidinyl)-8-azaspiro[4,5]decan-7,9-dione, 62.1 g of anhydrous sodium carbonate and 800 ml of dimethylformamide is stirred under nitrogen at 135° for 8 hours. It is allowed to cool to room temperature, filtered and the filtrate evaporated. The residue is poured with stirring and cooling into 300 ml of water, the mixture diluted with 1400 ml of water and filtered. The solids are triturated with 1600 ml of ethyl acetate and 10 ml of saturated aqueous sodium carbonate. The organic layer is separated, dried, evaporated and the residue dissolved in 1,000 ml of ethyl acetate. The solution is acidified with hydrogen chloride, the precipitate filtered off and recrystallized from aqueous methanol, to yield the 8-[1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-piperidinyl]-8-azaspiro[4,5]decan-7,9-dione hydrochloride melting at 277°-279° (dec.).

出典