Astrazeneca Ab

Ian Patel

Andrew D Jones

Maureen Young

Jonathan David Moseley

Evan William Snape

Philip Hopes

Ian Ashworth

Daniel Levin

A process is described for reacting a vinylogous amide with an &#x3b1;,&#x3b2;-unsaturated ketone in the presence of a silicon compound to form an 1,5-diketone which is converted to a 1,4-dihydropyridine. Asymmetric substituted 1,4-dihydropyridines are synthesized by the process by preparing an asymmetric vinylogous amide by reacting a 1,3-cyclohexanedione with a substantially homo-chiral phenylethylamine. Reaction of the asymmetric vinylogous amide with an &#x3b1;,&#x3b2;-unsaturated ketone in the presence of a silicon compound forms an asymmetric 1,5-diketone. The 1,5-diketone is converted to an asymmetric substituted 1,4-dihydropyridine.

Process for asymmetric synthesis of substituted 1,4 -dihydropyridines

Process for preparing 3-[(4S)-5-oxo-2-(trifluoromethyl)-1,4,5,6,7,8-hexahydroquinolin-4-yl]benzonitrile, pharmaceutical compositions containing the compound and methods of treatment using the same.

Method

A method for the synthesis of an &#x3b1;,&#x3b2;-unsaturated ketone useful for making substituted 1,4-dihydropyridines is described by reacting an aldehyde with pyrrolidine and then adding a ketone followed by trifluoroacetic acid at low temperature. The synthesis is used in a process for making substituted 1,4-dihydropyridines wherein a vinylogous amide is prepared by reacting a 1,3-cyclohexanedione with a phenylethylamine. The &#x3b1;,&#x3b2;-unsaturated ketone can be reacted with a vinylogous amide to form a 1,5-diketone which can be converted to a substituted 1,4-dihydropyridine.

Process for synthesis of alpha, beta-unsaturated ketones

Growing community of inventors

Bristol, United Kingdom

Ian Patel