تفاعل #214456

معادلة التفاعل

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

المذيبات

dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   ترشيحfiltered
2. 2
   أخرىthe filtrate evaporated
3. 3
   workup.ADDITIONThe residue is poured
4. 4
   workup.STIRRINGwith stirring
5. 5
   درجة الحرارةcooling into 300 ml of water
6. 6
   workup.ADDITIONthe mixture diluted with 1400 ml of water
7. 7
   ترشيحfiltered
8. 8
   أخرىThe solids are triturated with 1600 ml of ethyl acetate and 10 ml of saturated aqueous sodium carbonate
9. 9
   أخرىThe organic layer is separated
10. 10
    أخرىdried
11. 11
    أخرىevaporated
12. 12
    workup.DISSOLUTIONthe residue dissolved in 1,000 ml of ethyl acetate
13. 13
    ترشيحthe precipitate filtered off
14. 14
    أخرىrecrystallized from aqueous methanol

الإجراء التجريبي

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.).

المصدر