Patent ID: 7186827
Filing Date: 2007-03-06
Classification: A61P,C07D

Abstract:
1. A process of preparing a compound of the formula (I): wherein: Het is a monocyclic ring which is heterocyclic and contains at least the one nitrogen atom which is covalently attached to the carbonyl group; Ring a is: piperidinyl, hexahydropyrimidinyl, hexahydropyridazinyl, piperazinyl, 1,2-thiazinanyl-1,1-dioxide, 1,2,6-thiadiazinanyl-1,1-dioxide, morpholinyl, or thiomorpholinyl; each of ring a or Het is optionally substituted with one or more R R R said process comprising: a) reacting an allyl alcohol of the formula (II) with a vinyl ether of the formula (III) in the presence of a palladium catalyst and a ligand chosen from 1, 10-phenathroline, 4, 7-diphenyl-1, 10-phenathroline and 2,2′-dipyridyl at a temperature range of 20° C to 120° C., continuing the reaction for about 7 h at about 100–200° C.; where n in formula (III) is 2, 3, 4 or 5; b) in a one pot reaction, reducing an intermediate (V) and reacting (V) with a nitrogen containing heterocycle (VI) where one of the nitrogen atoms bears a reactive acyl group: —CO—X wherein X is a halogen atom, and subsequently further reacting with the product (IV) above, to yield as product intermediate (VII); subsequently reducing (VII) by asymmetric catalytic hydrogenation to provide ester (VIII); hydrolyzing intermediate (VIII) to produce the acid (IX): c) reacting the intermediate (IX) produced above with an amine intermediate bearing ring a under coupling conditions to produce (I): and subsequently isolating the product (I).