This review covers up to 2010 and some available references of 2011 of synthetic advances in the Biginelli reaction, including recent mechanistic advances, new building blocks, new pharmacological disclosures and asymmetric syntheses. Also present account is covering all aspects of the reaction whereas some of previous ones emphasized one aspect and others had passing reference.

Organic chemistry Z 0200 Biginelli Reaction -[recent advances with respect to mechanism, bulding blocks, catalyst variation and optimization; 168 refs.]. -(SAINI, A.; KUMAR, S.; SANDHU*, J. S.; J. Indian Chem. Soc. 84 (2007) 10, 959-970; Dep. Chem., Punjabi Univ., Patiala 147 002, India; Eng.) -H. Toeppel 28-236

6-[(Dimethylamino)methylene]amino-1,3-dimethyl uracil 1 undergoes formal [4+2] cycloaddition reaction with non conjugated imines to give pyrimido [4,5-d]pyrimidines 3. When reacted with conjugated imines and a,b-unsaturated nitro compounds cycloaddition also occurs leading to unexpected pyrido[2,3-d]pyrimidines 5 and 9, respectively. Pyrimido[4,pyrimidines and pyrido[2,3-d]pyrimidines are an important class of annulated uracils of biological significances because of their connection with purine and pteridine systems. 1 Several patents have been reported for the preparation of these fused heterocycles, derivatives which are useful as bronchodilators, 2 vascodilators, 2 antiallergic, 2,3 antihypertensive 4 and anticancer 2 agents and recently pyrimido[4,5-d] pyrimidine analogues of folic acid have been screened for antitumor activity 5 . Therefore, for the preparation of these complex molecules, there has been remarkable interest in the synthetic manipulations of uracils. 6 Also the synthetic exploitation of the nucleophilic double bond of uracil is an undeveloped field in view of a great variety of potential products. 7 There have been reports for direct functionalisation of uracil using the C 5 -C 6 double bond via thermolytic 8 and photocycloaddition reactions. 9 The heteroannulation of uracils usually require either forcing conditions 10 or relatively longer synthetic pathways. 11 In continuation of our studies on uracil analogues 12 we now want to present a new, simple and efficient preparation of novel fused pyrimidines based on [4+2] cycloaddition reaction by exploiting the 5-6 double bond of uracil in a onepot synthesis.A new approach to the synthesis of pyrimido[4,5-d]pyrimidines reported by Wamhoff et.al. 13 is the aza-Wittigtype reaction of iminophosphoranes of 5-aminouracils with aromatic isocyanates which leads to functionalised pyrimido[4,5-d]pyrimidines. Broom et al. 14 synthesised pyrido[2,3-d]pyrimidine from the reaction of DMAD and 6-aminouracil in protic solvent but obtained uncyclised condensed acetylenic adduct when the reaction was carried out in DMF. Also Wamhoff's group reported substituted pyrido[2,3-d]pyrimidines from 6-substituted uracil via [4+2] cycloaddition with electron-deficient olefins. 15 The main disadvantages in this method are the limitation to electron-deficient olefins and the low yield due to side reactions. Hirota et al synthesised pyrido [2,3-d]pyrimidines by the palladium-mediated C-C coupling reaction of electron-deficient olefins with uracil 1 in refluxing acetic acid, 16 but they used a stoichiometric amount of expensive Pd(OAc) 2 as a coupling reagent. Our synthetic strategy utilising non conjugated and conjugated imines and b-nitro styrenes with 6-[(dimethylamino)methylene]aminouracil affords an unprecedented one-pot synthesis of pyrimido[4,5-d]pyrimidines and pyrido[2,3-d]pyrimidines respectively in excellent yields. Scheme 16-[(Dimethylamino)methylene]amino-1,3-dimethyl uracil 1 was readily obtained by the reaction of 6-amino-1,3-dimethylbarbituric acid with (DMF-D...

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