Patent ID: 9029421
Filing Date: 2015-05-12
Classification: A61P,C07B,C07C

Abstract:
1. A process for preparing a compound of formula (VI) or a salt thereof the process comprising: (i) reacting 4-methoxyphenyl acetone with an amine of formula (VIII) under conditions of reductive amination to produce a compound of formula (II) or a salt thereof, wherein there is no isolation of an imine intermediate formed during the reductive amination and wherein the reductive amination is carried out in the presence of an ionic compound and a reducing agent, wherein the ionic compound is sodium acetate trihydrate and the reducing agent is sodium borohydride, (ii) condensing the compound of formula (II) or an acid addition salt thereof with an α-haloketone of formula (III) to produce a compound of formula (IV) (iii) reducing the compound of formula (IV) to a compound of formula (V), wherein the compound of formula (IV) in step (iii) is subjected to chiral reduction using a chiral reducing agent selected from the group consisting of (−)-DIP-chloride, β-isopinocamphinyl-9BBN (R-Alpine-Borane); a chiral β-oxoaldiminatocobalt (II) complex, a dioxazaluminium complex derived from amino acid esters, LiAlH4 and borane methyl sulfide, and dihydrooxazaborins; in the presence of a catalytic amount of a single enantiomer of an oxazaborolidine reagent derived from a chiral oxazaborolidine catalyst, and (iv) reducing the compound of formula (V) to the compound of formula (VI), wherein the reduction of step (iv) is carried out by either (1) a hydrogen donating compound in the presence of a hydrogen transfer catalyst or (2) ammonium formate using a hydrogenation catalyst, wherein R