Synthesis Methods of factor Xa inhibitors such as betrixaban and Pharmaceutical compositions containing the Free Base or Salt betrixaban substantially pure.

摘要

Claim 1: a method of preparation of a compound of the formula II or its Salts, comprising: contacting a compound of the formula II: a compound of the formula II - B: under reaction conditions to form the compound of formula II or its sa wherein: R1 and R2 are, MO DO IndependentAlkyl C1 - 6; R3 and R4 are selected independently of the group consisting of hydrogen, Fluorine, Chlorine, Bromine and methoxy; and R5 is selected from the group consisting of chlorine, Fluorine, Bromine, and methoxy.Claim 7: a method for the preparation of betrixaban, which has the formula I or one of its Salts, comprising: contacting a compound of the Formula with a compound of the formula: B: under reaction conditions to form betrixaban or its Salt.Claim 36: a method for the preparation of betrixaban, which has the formula I or one of its Salts, comprising: a) contacting a compound of the formula: D with a compound of the formula and reaction conditions including: in acetonitrile as SolventTo form a compound of the formula (C: b) exposure of the compound of formula c to reducing conditions comprising hydrogen gas, in the presence of a Catalyst.To form a compound of formula (B: c) contact of the compound of formula B with a compound of formula: in reaction conditions, comprising a coupling Reagent to form amide betrixaban or its Salt.