Patent ID: 6822093
Filing Date: 2004-11-23
Classification: C07D

Abstract:
A process of making a compound of the formula: wherein:W is CR3 or N, wherein R3 is chosen from hydrogen, C1-5alkyl, C1-5alkoxy, arylC0-5alkyl; Y is chosen from a bond, C1-4 saturated or unsaturated branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O, N, or S(O)m and wherein Y is optionally independently substituted with one to two oxo groups, phenyl or one or more C1-4 alkyl optionally substituted by one or more halogen atoms; wherein when Y is the carbon chain, the left side terminal atom of Y is a carbon; Z is chosen from: aryl, heteroaryl chosen from pyridinyl, piperazinyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, furanyl, thienyl and pyranyl, heterocycle chosen from tetrahydropyrimidonyl, cyclohexanonyl, cyclohexanolyl, 2-oxa- or 2-thia-5-aza-bicyclo[2.2.1]heptanyl, pentamethylene sulfidyl, pentamethylene sulfoxidyl, pentamethylene sulfonyl, tetramethylene sulfidyl, tetramethylene sulfoxidyl or tetramethylene sulfonyl, tetrahydropyranyl, tetrahydrofuranyl, 1,3-dioxolanonyl, 1,3-dioxanonyl, 1,4-dioxanyl, morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxidyl, thiomorpholinyl sulfonyl, piperidinyl, piperidinonyl, pyrrolidinyl and dioxolanyl, each of the aforementioned Z are optionally substituted with one to three halogen, C1-6 alkyl, C1-6 alkoxy, C1-3 alkoxy-C1-3 alkyl, C1-6 alkoxycarbonyl, aroyl, C1-3acyl, oxo, pyridinyl-C1-3 alkyl, imidazolyl-C1-3 alkyl, tetrahydrofuranyl-C1-3 alkyl, nitrile-C1-3 alkyl, nitrile, phenyl wherein the phenyl ring is optionally substituted with one to two halogen, C1-6 alkoxy or mono- or di-(C1-3 alkyl)amino, C1-6 alkyl-S(O)m, or phenyl-S(O)m wherein the phenyl ring is optionally substituted with one to two halogen, C1-6 alkoxy, halogen or mono- or di-(C1-3 alkyl)amino; or Z is optionally substituted with one to three amino or amino-C1-3 alkyl wherein the N atom is optionally independently mono- or di-substituted by aminoC1-6alkyl, C1-3alkyl, arylC0-3alkyl, C1-5 alkoxyC1-3 alkyl, C1-5 alkoxy, aroyl, C1-3acyl, C1-3alkyl-S(O)mâ€” or arylC0-3alkyl-S(O)mâ€” each of the aforementioned alkyl and aryl attached to the amino group is optionally substituted with one to two halogen, C1-6 alkyl or C1-6 alkoxy; or Z is optionally substituted with one to three aryl, heterocycle or heteroaryl as hereinabove described in this paragraph each in turn is optionally substituted by halogen, C1-6 alkyl or C1-6 alkoxy; or Z is nitrite, amino wherein the N atom is optionally independently mono- or di-substituted by C1-6alkyl or C1-3alkoxyC1-3alkyl, C1-6alkyl branched or unbranched, C1-6alkoxy, nitrileC1-4alkyl, C1-6 alkyl-S(O)m, aryl chosen from phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furanyl, thienyl and pyranyl each aryl being optionally substituted with one to three halogen, C1-6 alkyl, C1-6 alkoxy, di-(C1-3 alkyl)amino, C1-6 alkyl-S(O)m or nitrite, and phenyl-S(O)m, wherein the phenyl ring is optionally substituted with one to two halogen, C1-6 alkoxy or mono- or di-(C1-3 alkyl)amino; m=0, 1 or 2; said process comprising: i) in a one pot process, reacting a compound of the formula(C) with a Grignard reagent Râ€”Mgâ€”Xb followed by the addition of an E-Y-Z compound wherein Y-Z is as defined above, said E-Y-Z component is further characterized as being an electrophilic derivative of Y-Z, said reaction taking place in a methylene chloride at âˆ’78Â° C. to RT, for a reaction time of Â½ hour to 2 hours, and isolating the product compound; wherein:Xb is chosen from Br, Cl and I; R is chosen from aryl, C1-6alkyl and C5-7cycloalkyl.