| 主权项 |
1. A process for manufacturing a compound of formula 5, or a stereoisomer, tautomer, or a salt thereof, comprising the following steps: Step A: contacting a compound of formula B1 with a reaction mixture comprising a solvent selected from aromatic solvents, aliphatic solvents, halogenated solvents, polar aprotic solvents, ester solvents and ethereal solvents and an acid anhydride (R5C═O)2O, such that a compound of formula B2 is produced Step B: i) contacting a compound of formula B2 with a reaction mixture comprising a first solvent selected from aromatic solvents, aliphatic solvents, halogenated solvents, polar aprotic solvents, ester solvents and ethereal solvents, a first base selected from lithium amide, lithium dialkylamides, lithium alkoxides and isomers of butyllithium and optionally an alcohol additive, ii) contacting the mixture of step (i) with a second solvent selected from aromatic solvents, aliphatic solvents, halogenated solvents, polar aprotic solvents, ester solvents and ethereal solvents and a second base selected from isomers of butyllithium and Grignard reagents, iii) contacting the mixture of step (ii) with a boric acid derivative, iv) optionally contacting the mixture of step (iii) with a third solvent selected from aromatic solvents, aliphatic solvents, halogenated solvents, polar aprotic solvents, ester solvents and ethereal solvents and a third base selected from isomers of butyllithium and Grignard reagents and then contacting the resulting mixture with a boric acid derivative, and v) optionally contacting the mixture of step (iii) or step (iv) with water and acid, such that a compound of formula B3 is produced: Step C: contacting a compound of formula B3 with a reaction mixture comprising a solvent selected from aromatic solvents, aliphatic solvents, halogenated solvents, polar aprotic solvents, ester solvents, ethereal solvents and water, a base selected from acetates, phosphates and carbonates, a catalyst, and a compound of formula 3 such that a compound of B5 is produced Step D: contacting a compound of formula B5 with a reaction mixture comprising a solvent selected from aromatic solvents, aliphatic solvents, halogenated solvents, polar aprotic solvents, ester solvents, ethereal solvents and water and a reagent for the removal of the R5C(═O)— moiety selected from acids, bases and metal catalysts, such that a compound of formula 5 is produced; optionally followed by a salt forming reaction; wherein, W represents CH; R1 represents N-morpholinyl; R2 represents hydrogen; R3 represents trifluoromethyl; R4 represents hydrogen; and R5 is selected from the group consisting of (1) hydrogen, (2) substituted or unsubstituted alkyl, (3) substituted or unsubstituted alkyloxy, (4) substituted or unsubstituted aryl, (5) substituted or unsubstituted aryloxy, (6) substituted or unsubstituted arylalkyloxy; BY2 represents a boronic acid, an acyclic boronic ester, a cyclic boronic ester, or a trifluoroborate salt; and Hal represents halogen. |
