Pyrimido benzimidazol

Cyclocondensation of 3-trifluoroacetyl substituted lactams with cyclic 1,3-bisnucleophiles gives pyrimido[l,2-a]benzimidazoles 21 and l,2,4-triazoloI4,3-a]pyridines 22. The use of amidines yields pyrrolopyrimidines <95JCS(P1)2907 94H(37)915>. 

This ability to form hydroxy derivatives is more characteristic for dihydro-pyrimido[l, 2- ]benzimidazoles 158 and dihydropyrazolo[l, 5-<2]pyrimidines 159. Storing these solutions in chloroform, DMF or alcohols in air leads to the appropriate hydroxy derivatives 176 as a major product along with minor compounds 177 and 178 [158, 171, 172, 173, 174, 175] (Scheme 3.52). Often heterocycles like 176 were the only products of oxidation in air. Surprisingly,... 

An interesting approach for the synthesis of some fused pyrimidines has been reported by Shaaban [102] via reaction of 4,4,4-trifluoro-l-(thien-2-yl)butane-1,3-dione in the presence of triethylorthoformate with 5-aminopyrazole or 1,2,4-aminotriazole or 2-aminobenzimidazole under microwave irradiation. The resulting trifluoromethyl derivatives of pyrazolo[l,5-a]pyrimidine 56, l,2,4-triazolo[l,5-a] pyrimidine 57 and pyrimido[l,2-a]benzimidazoles 58 were obtained in excellent yields and purity (Scheme 42). 

The synthesis of a series of pyrimido[l,2-a]benzimidazoles 98 has been reported by Dandia and co-workers [136] through a MCR of 2-aminobenzimidazole, mal-ononitrile or ethylcyanoacetate and a carbonyl compound in water. Cyclic as well as acyclic carbonyl compounds could be used. The reaction highly benefits from microwave (domestic oven) irradiation in terms of rate and the compounds 98 were obtained in good yields (Scheme 75). 

Dandia A, Singh R, Jain AK et al (2008) Versatility of alternative reaction media water-mediated domino and green chemical synthesis of pyrimido[l, 2-a]benzimidazole under nonconventional conditions. Synth Commun 38 3543-3555... 

Amino-5-(2-hydroxy-benzoyl)-E9b/2, 170f. [2-(CO-NH2) 4H-chromon + Guanidin] 2-Benzyl-5-nitro- E9b/1, 33 [0HC-CH(N02)-CH0 + Ar—acetamidine] Pyrimido l,6-a]benzimidazol ... 

Neochoritis CG, Zarganes-Tzitzikas T, Tsoleridis CA et al (2011) One-pot microwave assisted synthesis under green chemistry conditions, antioxidant screening, and cytotoxicity assessments of benzimidazole Schifif bases and pyrimido[l, 2-a]benzimidazol-3(4H)-ones. Eur 1 Med Chem 46 297-306... 

The 2-aminobenzimidazole (525) serves as starting compound for the preparation of pyrimido(l, 2-a)benzimidazoles 325)2T> ... 

A number of heterocycles with bridged head nitrogen such as pyrazolo[l,5-a]pyrimidines 64, triazolo[l,5-a]pyrimidines 65, pyrimido[l,2-a]benzimidazole 66 and pyrimido-pyrazolo[3,4-6]pyridines 67 have been prepared. ... 

Diaminobenzimidazole reacts with chalcones on refluxing in DMF to yield pyrimido[l,2-fl]benzimidazoles [Eq. (100)] (86KGS1136 89KGS1071). The course and mechanism of this reaction are not fully clear, taking into account that the A-amino group must be considerably more active towards carbonyl compounds than the 2-amino group (cf. Section IV,C,3). 

Activated 2-benziiiiidazoles (2- CN, CO2R) react with a variety of A acylimidates imder microwave irradiation in open vessels to provide a new synthesis of pyrimido[l,6-a] benzimidazoles (SO) [94TI>IS63]. 

The pyrimidine ring was fused to a number of heterocycles with a bridge-head nitrogen when mixtures of enaminones 613 and heterocyclic amines 614, 615, or 616 were subjected to MWI for 10-20min. Thus, pyrazolo[l,5-u]pyrimidines 617, triazolo[l,5-a]pyrimidines 618, or pyrimido[l,2-u]benzimidazole 619 were obtained in 88-95% yields (Scheme 121). Those products required 0.5-6 h heating at reflux in absolute ethanol to give 70-80% yields (04JCR(S)174). 

The ring closure of 2-benzimidazoles 620 with A-acyl imidates 621 as jS-die-lectrophiles without a solvent in open vessels under MWI for 15-30 min led to pyrimido[l,6-u]benzimidazoles 622 in 38-86% yields (Scheme 121). In contrast, no ring closure occurred when compounds 620 (X = COOMe) and 621 (R = R = Me) were heated in toluene with continuous azeotropic elimination of water for 48 h 95% of 620 was recovered unchanged (94TL4563). 

In a closely related report, Obushak et al. extended the active methylene seope to another example of a 6,5-fused bicycle. Onee again, traditional Dimroth triazole synthesis conditions gave the desired triazole 37 from lH-benzimidazol-2-ylacetonitrile 36 and aryl azides en route to [ 1,2,3]triazolo-[4, 5 4,5]pyrimido[ 1,6-a]benzimidazole 38. 

Saleh et al. (2012) have developed a novel and efficient three-component condensation reaction of an aldehyde, amino azoles, and p-keto sulfone for the synthesis of pyrimido[l,2-a]benzimidazoles (143) and pyrazolo[3,4-b]pyridines (146) under ultrasonic irradiation via utilization of P-keto sulfone as an important synthon (Schemes 8.47 and 8.48). 

Saleh, T. S., Eldebss, T. M. A. and Albishri, H. M. 2012. Ultrasound assisted one-pot, three-components synthesis of pyrimido[l,2-a]benzimidazoles and pyrazolo[3,4-fc]pyridines A new access via phenylsulfone synthon. Ultrason. Sonochem. 19 49-55. 

A convenient and clean water-mediated synthesis of a series of 4-amino-2-ar-yl-1,2-dihydro pyrimido[l,2-a]benzimidazoles has been reported using alternative nonconventional energy sources [37]. The products were obtained in shorter times with excellent yields (78-89 %) from the multicomponent reaction of 2-ami-nobenzimidazole, malononitrile/ethylcyanoacetate, and carbonyl compounds (Scheme 8.26). The procedure does not involve the use of aity additional reagent/ catalyst, produces no waste, and represents a green synthetic protocol with high atom economy. The combination of microwave irradiation, ultrasonic irradiation, and aqueous-mediated conditions using multicomponent reactions leads to enhanced reaction rates, higher yields of pure products, easier workup, and sometimes selective conversions. Consequently, this protocol should be welcome in these environmentally aware days. 

To further improve the procedure, the reaction was also studied using cetyl trimethyl ammonimn bromide as a phase-transfer catalyst, but no change in yield was observed. Although the reaction time was reduced shghtly, it may be concluded that the aqueous medium is the perfect method for the synthesis of pyrimido[l,2-a]benzimidazoles. 

Similar testing was performed to predict the levels of 28 types of pharmacological activity in stmcturally similar condensed azole derivatives of the following chemical classes imidazoles, 1,2,4-triazoles, indoles, purines, benzimidazoles, imidazo[l,2-a]benzimidazoles, pyrimido[l,2-a]benzimidazoles, pyiazolo[l,5-a]benzimidazoles, pyirolo[l,2-a]benzimidazoles, l,2,4-triazolo[l,5-a]benzimidazoles, thiazolo[2,3-a]... 

Cl3H13N3O3, Methyl 1,2,3,4-tetrahydro-1-methyl-2-oxo-pyrimido[1,2-a]benzimidazol-4-carboxylate, 4OB, 249 Cl3H14N4OS, 6,6-Dimethyl-3-methylthio-6,7-dihydro-as-triazino[1,6-c]quinazolin-5-ium-1-olate, 4IB, 343 Cl3H15NO2, trans-1 -Hydroxy-spiro[pyrrolidine-2,2 -tetralin]-5-one, 45B, 311... 

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