4-Phthalimidobutyric acid → 2-[4-Oxo-4-[(2S)-2-(1-pyrrolidinylcarbonyl)-1-pyrrolidinyl]butyl]-1H-isoindole-1,3(2H)-dione

To a solution prepared by dissolving 1,17 g (5,0 mM) 4-phtalimido-butyric acid and 0,56 g (5,5 mM) triethylamin in 20 ml chloroform 0,61 g (5,0 mm) pivaloylchlorid were dropped at −15° C. under stirring. The reaction mixture was stirred for 1 hour at the above temperature and then a solution prepared by dissolving 1,03 g (5,0 mM) L-prolyl-pyrrolidin-hydrochloric acid salt in a mixture of 5 ml chloroform and 1,5 ml (1,1 g, 11,0 mM) triethylamine were dropwise added to it. Reaction mixture was stirred at room temperature for 4 hours, then it was washed successively with water, 30% cc. citric acid solution, saturated aqueous sodium bicarbonate solution, water and with saturated sodium chloride solution. The organic phase was dried on calcinated magnesium sulfate and it was evaporated. Crystallisation of the residue from a mixture of 5 ml chloroform and 10 ml petrolether yielded 1,1 g (53%) N-(4-phtalimido-butanoyl)-L-prolyl-pyrrolidin which melted at 148-149° C. The compounds of the general formula I were synthetised by the method as explained above starting from the corresponding compounds having general Formulas (II) and (III).

1. customTo a solution prepared
2. additionwere dropped at −15° C.
3. stirringThe reaction mixture was stirred for 1 hour at the above temperature
4. customa solution prepared
5. additionwere dropwise added to it
6. customReaction mixture
7. stirringwas stirred at room temperature for 4 hours
8. washit was washed successively with water, 30%
9. customThe organic phase was dried
10. customwas evaporated
11. customCrystallisation of the residue
12. additionfrom a mixture of 5 ml chloroform and 10 ml

ORD record

ord-1d45ed633a69433f8399d29a81146aca

Source dataset

uspto-grants-2001_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06191161B1