Compounds (Piran - piperidinil) becimidazol, Pharmaceutical composition that comprises, their use for preparing a drug for the treatment of disorders mediated by M1 receptor agonism, processes for preparing compounds useful as Intermediates in the synthesis of the same.

摘要

Compound (Piran - piperidinil) benzimidazole formula (1) or a Salt or solvate thereof where: R5 is selected from Halogen, alkyl of C1 C1 - 6 - 6, alkyl substituted with one or more Atoms of F, 6 - alkoxy C1, C1 6 - alkoxy substituted with one or more Atoms of F, Select between R6 and cyano Halo; Hydrogen, alkyl C1 C1 - 6 - 6, alkyl substituted with one or more Atoms of F, cycloalkyl C3 - 6C3-6 cycloalkyl substituted with one or more Atoms of F, 6 - alkoxy C1, C1 6 - alkoxy substituted with one or more Atoms of F, and cyano; and q is H or alkyl of C1 - 6. Its use for preparing Medicine useful for Treatment of conditions requiring M1 agonism or psychotic Disorders and Cognitive Impairment.Processes of preparing Said Compound intermediary compounds used in the same.Claim 1: a process for preparing a compound of formula (1) or a Salt or solvate thereof as defined in claim 1, wherein Said process is selected from: (A1) coupling processes comprising a compound of formula (2) with a compound of formula (3) OJ R5 'is a group of R5 as defined in claim 1,Group or a convertible in R5 and R6 is a group R6 are as defined in claim 1, or a group Convertible in R6,Under appropriate conditions for Reductive Alkylation process; and (A2) comprising reacting a compound of formula (2) with a compound of formula (3) in the presence of a source of cyanide to form the intermediate ciano (30) that can be made to react with a Grignard Reagent of alqui The qmgx to form compounds of formula (1).Where R5 'is a group of R5 as defined in claim 1, or a group Convertible in R5 and R6 is a group R6 are as defined in claim 1, or a group Convertible in R6,And Q is C1 - 6 h or alkyl Grignard reactions under conditions appropriate for the process; and (b) that includes coupling a compound of formula (4) with a compound of formula (5) where R5 'is a group of R5 as defined in claim 1, or a group Convertible in R5 and R6 is a Group R6 as Defined in claim 1, or a group Convertible in R6,And Q is C1 - 6 H and alkyl; X and y represent the two groups outgoing optionally in an Inert Solvent, optionally in the presence of a base, optionally with Warming process; and (c) comprising treating a compound of formula (6) with a catalyst of Palladium or COPPER (vii) pa Ra an intramolecular cyclization.Where R5 'is a group of R5 as defined in claim 1, or a group Convertible in R5 and R6 is a group R6 are as defined in claim 1, or a group Convertible in R6, and q is H or alkyl of C1 - 6; and Z is a leaving Group such as BR rCL or triflate or process; (d) coupling comprising a compound of formula (7) with a compound of formula (9) where R5 'is a group of R5 as defined in claim 1, or a group Convertible in R5 and R6 is a group R6 as defined in claim 1 in a Group, or convertible R6,And Q is C1 - 6 h or alkyl; and R is an alkyl group C1 - 5 by heating in an Inert Solvent, e.g., xylene, followed by reduction of the double Bond of piperidine; and (e) process comprising reacting a compound of formula (10) with a Reagent / Combination of Reagents to perform The Curtius rearrangement of compound (10),Followed by intramolecular cyclization; where R5 'is a group of R5 as defined in claim 1, or a group Convertible in R5 and R6 is a group R6 are as defined in claim 1, or a group Convertible in R6,And Q is H or alkyl of C1 - 6; and (f) coupling process comprising a compound of formula (11) with a compound of formula (12) where R5 'is a group of R5 as defined in claim 1, or a group Convertible in R5 and R6 is a group R6 as defined in claim 1, or Group Co Nvertible R6,Q is H or alkyl of C1 - 6 and Z is Hydroxy or a leaving Group in terms of Alkylation reaction or Mitsunobu and Optionally, after that, for any of the above processes: Remove any Protective Group; and / or convert a compound of formula (1) or a Salt or solvate thereof In another Compound of formula (1) or a Salt or solvate thereof.Claim 1: a compound used as Intermediate in the process according to claim 1,Wherein is selected from: a compound of formula (2) or a Salt or solvate thereof; a compound of formula (30) or a Salt or solvate thereof; a compound of formula (4) or a Salt or solvate thereof; a compound of formula (6) or a Salt or solvate of the same; or a compound of fo Formula (10) or a Salt or solvate thereof; where R5 'is a group of R5 as defined in the reivindApplication 1, group or a convertible in R5 and R6 is a group R6 are as defined in claim 1, or a group Convertible in R6, Q is H or alkyl of C1 - 6, and Z is a leaving Group.