Preparation of imidazo[1,2-c]pyrimidinones from a chloropyrimidine and an electron poor ω-allylic amine

Abstract

Synthesis of the title ring system by a sequential intermolecular nucleophilic displacement and intramolecular 'conjugate' addition has been achieved both as a one pot and as a stepwise procedure; an X-ray structure determination has been carried out to distinguish between the possible isomeric structures 8c-I and 8c-II.The alkenylamidopyrimidines 1 were identified as key starting materials in an on-going project to prepare ring fused diazepines.

Pyrimidine annelated heterocycles - synthesis and cycloaddition of the first pyrimido[1,4]diazepine N-oxides

“…Pyrimido [1,4]diazepine N-oxides have been prepared for the first time and the cycloadditive ability of 3 has been shown to be dependent on the degree of substitution at the C-atom of the dipole. The aldonitrone 3a reacts with both olefinic and acetylenic substrates whilst the C-substituted dipole 3b is inactive to olefinic dipolarophiles.…”

“…The starting aldehyde 5a and the proposed oxime 4a both have a high density of functionality and imidazopyrimidines 12a,b can arise from these substrates by cyclisation of the nucleophilic pyrimidine nitrogen atom onto the pendant electrophilic alkene. 4 The oxime 4 has two further channels for reactivity, viz. tautomerisation to the corresponding NH-dipole 13 with subsequent cycloaddition to 14 [intramolecular oxime olefin cycloaddition, IOOC, Fig.…”

“…8,9-Dihydro-7H-pyrimido [4,5-e] [1,4]diazepine N 6 -oxides, 3, were the target nitrones and their synthesis from (alkenylamino)pyrimidines 5 was envisaged (Scheme 1). Similar substrates have been widely investigated by Noguchi's group in their comprehensive study of the preparation of fused azepine rings by intramolecular thermal ene reactions (carbonyl, imine or hydrazone).…”

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5-Formyl-and 5-acetyl-4-(alkenylamino)pyrimidines 5 have been prepared as precursors to novel pyrimido [1,4]diazepine N-oxides 3. In addition to cyclisation to the targeted dipoles the substrates 5 have also been observed to form imidazopyrimidines 12 and 39 via an intramolecular Michael addition; additionally 5b has been observed to form the pyrimidoazepinone 42.

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New Imidazo[1,2‐c]pyrimidin‐5(6H)‐Ones Derived from Cytosine: Synthesis, Structure, and Cytotoxic Activity

“…To the best of our knowledge, only one analogous structure of imidazo(1,2‐ c )pyrimidin‐5(6 H )‐one derivate in position 8 by a carbon atom the 3,4‐etheno‐5‐methoxymethyl‐2′‐deoxycytidine has been reported so far. Other two partially saturated compounds as for example N ‐methyl‐6‐(2‐chloroethyl)‐5,7‐dioxo‐1,2,3,5,6,7‐hexahydroimidazo[1,2‐ c ] pyrimidine‐8‐carboxamide or methyl 2‐(1‐benzyl‐8‐formyl‐7‐methoxy‐5‐oxo‐1,2,3,5‐tetrahydroimidazo[1,2‐ c ]pyrimidin‐3‐yl)acetate and two compounds with fused aromatic rings that resemble the structural motif of 3a were also found within the crystallographic database. Typical interatomic separations and angles for each functional group are present within the structure of 3a .…”