2-Amino-5-cyanopyridine → 2-(5-Bromofuran-2-yl)-imidazo[1,2-a]pyridine-6-carbonitrile

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Reaction Steps

Referring now to Scheme 2, the acetate salt of 2-[5-(4-Amidinophenyl)-furan-2-yl]-5,6,7,8-tetrahydro-imidazo[1,2-a]pyridine-6-carboxamidine (7) was synthesized from 2-[5-(4-Cyanophenyl)-furan-2-yl]-imidazo[1,2-a]pyridine-6-carbonitrile (4a), through the bis-O-acetoxyamidoxime followed by hydrogenation in glacial acetic acid. Compound 4a was obtained in four steps starting with two successive brominations of 2-acetylfuran first with N-bromosuccinimide, and second with bromine to form 2-Bromo-1-(5-bromofuran-2-yl)-ethanone (2) in a moderate yield. A condensation reaction between 6-Amino-nicotinonitrile and compound 2 gave 2-(5-Bromofuran-2-yl)-imidazo[1,2-a]pyridine-6-carbonitrile (3a). A subsequent Suzuki coupling of 3a with 4-Cyanophenyl boronic acid furnished 4a in good yield. Interestingly, 2-[5-(4-Amidinophenyl)-furan-2-y]-imidazo[1,2-a]pyridine-6-carbox-amidine acetate salt (8a) was obtained from 4a, through the bis-O-acetoxyamidoxime followed by hydrogenation in a mixture of ethanol/ethylacetate. Thus, by choice of hydrogenation solvent the saturated or unsaturated imidazo[1,2-a]pyridine can be obtained.

Provenance & Evidence