Patent ID: 6344558
Filing Date: 2002-02-05
Classification: A61P,C07C,C07D

Abstract:
A method of preparing a 1-phenyl-3-dimethylaminopropane compound corresponding to formula whereinX represents OH, F, Cl, H or an OCOR6 group in which R6 is a C1-3-alkyl group; R1 is a C1-4-alkyl group; R2 represents H or a C1-4-alkyl group, and R3 represents H or a straight chain C1-4-alkyl group, or R2 and R3 together form a C4-7 cycloalkyl radical; when R5 represents H, R4 represents: (A) meta-Oâ€”Z, wherein Z is H, C1-3-alkyl, PO(OC1-4alkyl)2, CO(OC1-5-alkyl), CONHâ€”C6H4â€”(C1-3-alkyl) or COâ€”C6H4â€”R7, in which R7 is ortho-OCOC1-3-alkyl or meta- or para-CH2N(R8)2, where R8 is C1-4-alkyl or 4-morpholino, or (B) meta-Sâ€”C1-3-alkyl, meta-Cl, meta-F, meta-CR9R10R11, ortho-OH, ortho-Oâ€”C2-3-alkyl, para-F or para-CR9R10R11, where R9, R10 and R11 independently represent H or F; when R5 represents para-Cl, para-F, para-OH or para-Oâ€”C1-3-alkyl, R4 represents meta-Cl, meta-F, meta-OH or meta-Oâ€”C1-3-alkyl; or R4 and R5 together represent 3,4-OCH&boxH;CHâ€” or 3,4-OCH&boxH;CHOâ€”, as diastereoisomers or enantiomers in the form of free bases; said method comprising: (1) reacting a compound of formula I in which X represents Cl with at least one substance selected from the group consisting of zinc borohydride, zinc cyanoborohydride and tin cyanoborohydride to form a final compound in which X represents H; (2) reacting a compound of formula I in which X represents OH with dimethylaminosulfur trifluoride in a solvent to form a final compound in which X represents F; (3) reacting a compound of formula I in which X represents OH with thionyl chloride to form a final product in which X represent Cl; (4) reacting a compound of formula I in which X represents OH or with an acid chloride Clâ€”COOR6 to form a final compound in which X represents OCOR6; or (5) reacting a &bgr;-dimethylaminoketone of formula II with an organometallic compound of formula III in which Z represents MgCl, MgBr, MgI or Li to form a final compound in which X represent OH; andoptionally converting a free base into a salt with a physiologically acceptable acid.