Reaktion #411630

Reaktionsgleichung

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

Lösungsmittel

N,N-dimethylformamide

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction mixture was partitioned between water and ethyl acetate
2. 2
   SonstigeThe organic layer was collected
3. 3
   Trocknendried over magnesium sulphate and solvent
4. 4
   Sonstigeevaporated under reduced pressure
5. 5
   SonstigePurification
6. 6
   Wascheneluting with 9:1 dichloromethane/methanol
7. 7
   SonstigeThe product obtained
8. 8
   Temperaturheated at 100° C. for 2 h
9. 9
   SonstigeThe solvent was removed under reduced pressure
10. 10
    SonstigePurification
11. 11
    Wascheneluting with dichloromethane/methanol

Vorschrift

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.

Quelle