Pyrimido azepine-3-carboxylates

Bicyclic pyrimidin-4-ones (1100, R = H, n = 0-3 R = Me, n = 1) were also prepared from the appropriate lactim ether and EMME in the presence of ammonia or ammonium acetate [73JAP(K)34897 75MIP1]. Pyrimido[l,2-a]azepine-3-carboxylates (1100, R = H, Ph n = 2) were prepared in the reaction of 7-aminotetrahydro-2//-azepines (R = H, Ph n = 2) and EMME or in the reaction of O-methylcaprolactim and diethyl aminomethylenemalonate in ethanol [73JAP(K)34897 75MIP1]. 

The cyclocondensation of 2-amino-3//-azepine and EMME in boiling butanol for 1 hr gave a roughly 3 1 mixture of the isomeric 4//, 10//-and 4//,6//-pyrimido[l, 2-a]azepine-3-carboxylates (1155 and 1156) in 68% yield. The isomers could be separated by fractional crystallization. 4H-6//-Pyrimido[l,2-a]azepine-3-carboxylate (1156) was probably formed from the 4H,]0H isomer (1155) in a symmetry-allowed [ 1,5]-sigmatropic shift (84H2285). 

The 3-carbazoyl group of pyrimido[l,2-a]azepine 462 was acylated at N-2 with benzoyl chloride, or reacted with aldehydes, isocyanates, or isothiocyanates (77MI1). 3-Bromohexahydropyrimido[l,2-fl]azepin-4-one was obtained from the 3-carboxylic acid 415 (R = = H, R = COOH) in the... 

Wamhoff and Hendrikx prepared pyrimido[4,5-h]azepine-6-carboxylic acid derivatives 514 and 515 from carbodiimide 513 by reacting it with 5% sodium hydroxide solution or with hydrazine and i-propylamine in boiling... 

Demethoxycarbonylation of methyl 3,6-di-/-butyl-3//-azepine-l-carboxylate by DBU in xylene gives a mixture of not only the corresponding 3,6-di-t-butyl-3//-azepine, but also the 2/f-azepine and 4/f-azepine isomers <94JCS(P1)1753>. When heated in toluene at I25°C the 2H- and 3//-azepines are each converted quantitatively into azepine mixtures consisting of 2H-, 2>H-, and 4//-azepines in the ratios 12 51 1 (from the 2/f-isomer) and 12 56 1 (from the 3//-isomer). The distribution of the azepine isomers is proportional to their relative thermal stabilities as they interconvert via an allowed 1,5-hydrogen shift. Under similar conditions, methyl 2,5-di-/-butyl-3//-azepine-l-car-boxylate gives only the 3//-tautomer. Similar thermal tautomerizations of 3-phenyl-3//-azepine to 7-phenyl-3//-azepine <89H(29)253> and ethyl 4-oxo-4//,10//-pyrimido[l,2-a]azepine-3-carboxylate <84H(22)2285> to the 4//,6//-tautomer have been observed. 

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