Indian Journal of Chemistry Vol. 44B, August 2005, pp. 1653-1658 Syntheses of 1,3-disubstituted-5a-hydropyrrolo[2,3-d]quinazolino[3,2-e]pyrimidin- 6(5H)-ones: A comparison of conventional and microwave technique Cicily Augustine & Y K Agrawal* Institute of Pharmacy & Science, Nirama University of Science and Technology, Gandhinagar-Sarkhej Highway, Ahmedabad 382 481, India. Email -drykagrawal@yahoo.com Received 26 July 2004; accepted (revised) 27 December 2004 An exclusive new ring system of 1,3-disubstituted-5a-hydropyrrolo[2,3-d]quinazolino [3,2-e]pyrimidin-6(5H)-ones 4 has been synthesised from 4-chloropyrrolo[2,3-d]pyrimidines 2 which are prepared using phase transfer catalysts. The synthesis 4 highlights a comparative study of the conventional and microwave technique. Keywords: Hydropyrrolo-quinazolinopyrimidines, 4-chloropyrrolo[2,3-d]pyrimidines, microwave technique IPC: Int.Cl.7 C 07 D A development that had a profound impact on solvent-less solid phase organic syntheses is the use of microwave irradiation technique for the acceleration of the rate of organic reactions. Recent developments 1 in microwave enhanced reaction under solvent-free conditions involve the exposure of neat reactants to microwave irradiation. The salient features of these high yielding eco-friendly green protocols are the enhanced reaction rates, greater selectivity and experimental ease of manipulation. The advantages of a microwave enhanced solvent-free organic reactions over the conventional solution phase reactions are the good dispersion of active reagent sites, associated selectivity and easier work-up. A wide range of pharmacological properties have been attributed to the microwave synthesised angular as well as linear polycyclic condensed pyrrolopyrimi- dine moieties. For instance linear compounds, pyri- midopyridoindoles were used as antifertility drugs 2 , polymethylenethienodihydropyrrolopyrimidine showed fungicidal activity 3 , benzothienopyrimidines were used as tuberculostatic 4 and pyranothienopyrimidine as antispasmodic 5 . Tetracyclic linear diaminopyrrolo- pyrimidines, a confirmationally restricted analogue of trimethoprim proved to be potential dihydrofolate reductase inhibitors 6 . Similar to linear tetracyclic molecules certain activities were attributed to angular polycyclic molecules. Heterocyclopyrroloquinazoline were tested as antiarrhythmics 7 . Alkyl dihydrothioxo- pyrimidopyrimidoindole derivatives were screened as central nervous system stimulants as well as potential analgesics 8-10 , and indoloquinazolinones showed antimicrobial 11 effect whereas its analogue fluoro- indoloquinazolidinone demonstrated tuberculostatic activity 12 . In continuation of our interest in microwave assisted reactions 13-15 , to synthesise fused pyrimidines and looking at the various utility of microwave it was thought of to explore the use of microwave in synthe- sizing the new tetracyclic ring system of 1,3-disubsti- tuted-5a-hydropyrrolo[2,3-d]quinazolino[3,2-e]pyrimi- din-6(5H)-ones-4. Furthermore, the required 5,7- disubstituted-4-chloro-7H-pyrrolo[2, 3-d]pyrimidines 2 were obtained by chlorination of 5,7-disubstituted- 7H-pyrrolo[2,3-d]pyrimidine-4(3H)-ones 1 using phosphorous oxychloride along with a molar quantity of phase transfer catalysts containing chlorine ion. When the chlorination was performed in the presence of PT-catalysts containing chlorine such as tetrabutylammonium chloride (TBAC) or triethyl- benzylammonium chloride (TEBA) the yields of 2 were increased and reaction time decreased appreciably (Scheme I). The chlorination using PT- catalyst was completed within 3-4 hr 16 as compared to the chlorination in absence of catalyst, which required 12-14 hr 17 . The nucleophilic substitution of chlorine in 2 is important for the introduction of various reactive functionalities at position-4 of pyrimidine