Pyrimido azepines reactions

Reaction of 3-formyl-2-[A-(2-alkenyl)-A-benzylamino]-4//-pyrido[l, 2-n]-pyrimidin-4-ones 252 and primary amines in the presence of MS (4 A) afforded pyrido[l, 2 l,2]pyrimido[4,5-Z)]azepin-6-ones 253 (96T13081). 

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]. 

Additionally, uracil 6-iminophosphorane, isocyanate, and o-methyl-e-caprolactim ether join to form the intensely yellow pyrimido[4 5 4,5] pyrimido[6,l-n]azepine (360), as shown in Scheme 130. Upon ring closure, methanol is spontaneously eliminated. Diethyl azodicarboxylate affords with the other components pyrimido[4,5-e][l,2,4]triazoline (361), which is closely related to the alkaloid isofervenuline. The imidazo[5, -/][ ,2,4]tria-zine (362) results in a known Michael-type rearrangement sequence by treatment with diethyl acetylenedicarboxylate (86JOC149, 86JOC2787) in this latter case, the Michael-type addition occurs much faster than the expected three-component reaction [93H(35)1055]. 

In the first part of the section on the pyrimido[l,2-a]azepines, the chemistry of 2,3,4,6,7,8,9,10-octahydropyrimido[l,2-a]azepine (8) (generally called diazabicyclo[5.4.0] undec-7-ene, or DBU) is treated in a separate subsection, since DBU has proved to be a useful reagent in synthetic organic chemistry and an important catalyst in the synthesis of macromolecules. Since the appearance of two early reviews (72S591 75MI5), the applications of DBU have rapidly increased because of its favorable nonnucleophilic, yet strongly basic, properties. It can therefore be applied for the preparation of even relatively sensitive molecules. Following this, the synthesis, reactions, physicochemical properties, and briefly the applications of further pyrimido[l,2-a]azepine derivatives are discussed. The treatment of the chemistry of the other pyrimidoazepines (2-5 and 7) follows an essentially identical pattern to that for the pyrimido[l,2-a]azepines. 

The reaction of 2-amino-3//-azepine with diethyl ethoxymethylenema-lonate in boiling butanol for 1 hr gave a 6 1 mixture of ethyl 4-oxo-4W, 10//-pyrimido[l,2-fl]azepine-3-carboxylate (412) and ethyl 4-oxo 4H,6H-pyrimido[l,2-fl]azepine-3-carboxylate (413) (84H2285). 

Granik et al. prepared pyrimido[l,6-enamino amide 487 with diethyl acetals of dimethylformamide or dimethylacetamide in refluxing ethanol (80KGS1120). Compound 488 (R = H) was also obtained from enamino amide 487 in 61% yield by reacting it with triethyl orthoformate in refluxing acetic anhydride. 

The reaction of caprolactam with a mixture of formamide and phosphoryl chloride in a sealed tube at 120"C for 12 hr alforded 6,7,8,9-tetrahydro-5//-pyrimido[4,5-h]azepine (493) in 7% yield (70TL861 73BCJ2835). 

Pyritnidinediones 78 were found to undergo intramolecular ene reaction to afford pyrimido[4,5-6 azepine derivatives 80 [94JCS(P1)565]. 

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