تفاعل #411630

معادلة التفاعل

product

(±)-5-[9,10-Dihydro-4-hydroxy-2,7-dimethyl-4H-benzo[5,6]cyclohepta[1,2-d]thiazol-4-yl]-2,4(1H,3H)-pyrimidinedione

sodium hydride

1-(2-chloroethyl)pyrrolidine hydrochloride

→

subtitle product

(±)-5-(2,7-Dimethyl-4H-benzo[5,6]cyclohepta[1,2-d]thiazol-4-yl)-1-(2-(N-pyrrolidinyl)ethyl)-2,4(1H,3H)-pyrimidinedione

المذيبات

N,N-dimethylformamide

acetic acid

ظروف التفاعل

المعالجة

1. 1
   أخرىThe reaction mixture was partitioned between water and ethyl acetate
2. 2
   أخرىThe organic layer was collected
3. 3
   تجفيفdried over magnesium sulphate and solvent
4. 4
   أخرىevaporated under reduced pressure
5. 5
   أخرىPurification
6. 6
   غسيلeluting with 9:1 dichloromethane/methanol
7. 7
   أخرىThe product obtained
8. 8
   درجة الحرارةheated at 100° C. for 2 h
9. 9
   أخرىThe solvent was removed under reduced pressure
10. 10
    أخرىPurification
11. 11
    غسيلeluting with dichloromethane/methanol

الإجراء التجريبي

The product from example 18 step (ii) (1.44 g) was dissolved in dry N,N-dimethylformamide (20 ml) and treated cautiously with sodium hydride (60% dispersion by wt, 0.5 g) under nitrogen. After 10 min 1-(2-chloroethyl)pyrrolidine hydrochloride (0.8 g) was added and the whole heated at 50° C. for 16 h. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was collected, dried over magnesium sulphate and solvent evaporated under reduced pressure. Purification was by flash chromatography eluting with 9:1 dichloromethane/methanol. The product obtained was dissolved in acetic acid (10 ml) and heated at 100° C. for 2 h. The solvent was removed under reduced pressure. Purification was by flash chromatography eluting with dichloromethane/methanol mixtures to give the subtitle product as pale yellow foam.

المصدر