Preparation of citalopram useful as anti-depressant drug involves conversion of 5-halogenated compound to a 5-carboxylic acid intermediate followed by a reaction with dehydrating agent and sulfonamide or 5-amide derivative

摘要

Preparation of citalopram (I) involves conversion of a 5-halogenated compound (II) to a 5-carboxylic acid intermediate (III) followed by conversion of (III) to (I). - Preparation of citalopram (1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydro-5-isobenz ofurancarbonitrile) (I) involves conversion of 5-halogenated compound of formula (II) to a 5-carboxylic acid intermediate of formula (III) followed by conversion of (III) to (I). - Z = halo. - An INDEPENDENT CLAIM is included for the preparation of compounds of formula (III) and (V). - X = halo, CN, OR5, SR6 or NR7R8; - R5, R6 = 1-6C alkyl, (hetero)aryl or benzyl (all optionally substituted with T); - T = halo, 1-4C alkyl, cyano, -OH, 1-4C alkoxy, trifluoromethyl, nitro, amino, mono- or di-(1-4C)alkylamino; - Y = O, S or NR9; and - R7-R9 = R5 or H. - ACTIVITY - Antidepressant. - MECHANISM OF ACTION - Serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor. - No biological data given.