Imidazo pyrimidine, rearrangement

The pyrimido[2,l+][l,3]oxazine 322 rearranged into the imidazo[l,2- ]pyrimidine 323 on heating in DMF in the presence of benzoic acid (Equation 35) <2000NN1381>. 

The reaction with pyridone (167) was interpreted as proceeding by the formation of the pyridone (168), followed by the Smiles rearrangement leading to the spiro compound (169), which by ring opening provides the pyrimidine derivative (170). In a subsequent cyclization step the pyrido-[1,2-aJpyrimidine skeleton (171) is formed, and finally hydrolysis of the imino group leads to the 6-oxo derivative (172). In the homologous imidazo-[l,2-n]pyridine series, the 5-iminoimidazo[l,2-c<]pyridine intermediate of type (171) could be isolated. 

The presence or absence of the dioxolane protecting group in dienes dictates whether they participate in normal or inverse-electron-demand Diels-Alder reactions.257 The intramolecular inverse-electron-demand Diels-Alder cycloaddition of 1,2,4-triazines tethered with imidazoles produce tetrahydro-l,5-naphthyridines following the loss of N2 and CH3CN.258 The inverse-electron-demand Diels-Alder reaction of 4,6-dinitrobenzofuroxan (137) with ethyl vinyl ether yields two diastereoisomeric dihydrooxazine /V-oxide adducts (138) and (139) together with a bis(dihydrooxazine A -oxide) product (140) in die presence of excess ethyl vinyl ether (Scheme 52).259 The inverse-electron-demand Diels-Alder reaction of 2,4,6-tris(ethoxycarbonyl)-l,3,5-triazine with 5-aminopyrazoles provides a one-step synthesis of pyrazolo[3,4-djpyrimidines.260 The intermolecular inverse-electron-demand Diels-Alder reactions of trialkyl l,2,4-triazine-4,5,6-tricarboxylates with protected 2-aminoimidazole produced li/-imidazo[4,5-c]pyridines and die rearranged 3//-pyrido[3,2-[Pg.460]

Distillation of l,2,3,4-tetrahydropyrido[3,2-ii]pyrimidine-2,4-dione (384) with zinc dust caused a reductive rearrangement to imidazo[4,5-h]pyridine (385) (56JCS1045). Reaction of 6-chloropyrido[2,3-h]pyrazines (386) with potassium amide in liquid ammonia resulted in attack at C-2 giving (387), with ring contraction to (388) involving loss of chlorine to give imidazo[4,5-h]pyridine or 2-substituted derivatives thereof (389) (79JHC305). 

Combinations of N- and 5-alkylation in 2-imidazoline-2-thiols can lead to 5,6-dihydro-4//-imidazo[2,l-6]thiazoles when the heterocycles are treated with ketones in the presence of a halo-genating agent. This is a variant of the Hantzsch thiazole synthesis <92SC1293>. A further example of A-acylation in combination with nucleophilic substitution is the conversion of 2-chloro-2-imi-dazoline into (131) when it is treated with pyridine and an aryl isocyanate <87JCS(P1)1033>. 2-Imidazolines like clonidine are also known to A-nitrosate <93JCS(P2)59l>. Intramolecular alkylation is exemplified in the base-induced rearrangement of 2,5-diaryl-4-chloromethyl-2-imidazolines (132) into pyrimidines (Scheme 64) <93JOC6354>. 

A method for activation is the introduction of an additional nitrogen atom into the six-membered ring, as, for example, in the imidazo[l,2-fljpyrazine, imidazo[l,2-a]pyrimidine (7), or imidazo[l,2-c]pyrimidine (10) systems. Because of its electron-withdrawing property, the extra aza group of the last two systems activates the 5-position for base-catalyzed Dimroth rearrangement. 

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