Azaindole derivatives

Five-, Six-, and Seven-membered Lactim Ethers. Methods of Synthesis and Chemical Properties. (Review)

“…The N-substituted lactams 99 were synthesized by heating the lactim ethers from lactams 1-3 with halogen derivatives 98 in DMF or without a solvent and gave yields of 64% in the case of the chloride (boiling in DMF) [77] and 87-98% in the case of the bromides or iodides (60-100°C, 1-6 h) [3]. The reaction with the iodide (MeO 2 C) 2 CH(CH 2 ) 2 I was conducted at 110°C in an atmosphere of nitrogen [129].…”

“…Unsubstituted and also methoxycarbonyl-or ethoxycarbonyl-substituted lactim ethers react readily with derivatives of cyanoacetic acid and malononitrile, forming the corresponding products 68 with moderate (53-70%) or high (75-98%) yields. The reactions with the esters [7,77,78] and amide [77,79] of cyanoacetic acid are usually carried out at 80-120°C for 1-24 h. With R 1 = Me, R 2 = H, and X = COOMe the product 68 was obtained with a yield of 90% after 1 h at only 20°C [73]. Reaction with the amide [80] and substituted amides of cyanoacetic acid and also with the amide of cyanothioacetic acid [81] takes place when the reagents are boiled in DMF (3 h).…”

Study of reactions of lactim ethers with cyanoacetohydrazide

“…Using compound 12c as an example, it was demon strated that brief heating in 25% sulfuric acid leads to saponification of the cyano group to form the correspond ing carboxylic acid (13), which under these conditions undergoes decarboxylation giving rise to 3 [(azepan 2 ylidene)methyl] 5,6,7,8 tetrahydro [1,2,4]triazo lo[4,3 a]pyridine (14). On the whole, this behavior is not typical of usual enaminonitriles and is, apparently, attrib uted to the strong electron withdrawing effect of the triazolyl group (see Scheme 5).…”