반응 #214456

반응 방정식

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

용매

dimethylformamide

반응 조건

후처리

1. 1
   여과filtered
2. 2
   기타the filtrate evaporated
3. 3
   workup.ADDITIONThe residue is poured
4. 4
   workup.STIRRINGwith stirring
5. 5
   온도cooling into 300 ml of water
6. 6
   workup.ADDITIONthe mixture diluted with 1400 ml of water
7. 7
   여과filtered
8. 8
   기타The solids are triturated with 1600 ml of ethyl acetate and 10 ml of saturated aqueous sodium carbonate
9. 9
   기타The organic layer is separated
10. 10
    기타dried
11. 11
    기타evaporated
12. 12
    workup.DISSOLUTIONthe residue dissolved in 1,000 ml of ethyl acetate
13. 13
    여과the precipitate filtered off
14. 14
    기타recrystallized from aqueous methanol

실험 절차

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.).

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