| 摘要 |
Provided herein are novel, commercially viable and industrially advantageous processes for the preparation of benzofuran-2-carboxamide derivatives and their intermediates, or a pharmaceutically acceptable salt thereof, in high yield and purity. Provided particularly herein are novel, commercially viable and industrially advantageous processes for the preparation of vilazodone or a pharmaceutically acceptable salt thereof in high yield and purity. Provided also herein is an improved and commercially viable process for the preparation of 3-(4-hydroxybutyl)-1H-indole-5-carbonitrile, in high yield and purity, using novel intermediate compound 3-(4-hydroxybutyryl)-1H-indole-5-carbonitrile. |
| 主权项 |
1. A process for the preparation of a benzofuran-2-carboxamide derivative of formula I: or a pharmaceutically acceptable salt thereof, wherein R is H, a protecting group ‘P’, or an ‘IND-Q-’ radical, wherein IND is an indol-3-yl radical, a 2,3-di-hydro-1H-indol-3-yl radical, or a 2-oxo-2,3-di-hydro-1H-indol-3-yl radical, which is unsubstituted or mono- or polysubstituted by OH, OA, CN, X, COR1 or CH2R1; Q is selected from —(CH2)2—, —(CH2)3—, and —(CH2)4—; A is an alkyl group having 1 to 6 carbon atoms; X is F, Cl, Br or I; R1 is OH, OA, NH2, NHA or NA2; which comprises: amidation of a benzofuran-2-carboxylic acid ester derivative of formula II: or a salt thereof, wherein R is as defined in formula I, and R2 is an alkyl group having 1 to 4 carbon atoms; with ammonia in a suitable solvent to produce the benzofuran-2-carboxamide compound of formula I, and optionally converting the compound of formula I obtained into a pharmaceutically acceptable salt thereof, wherein the ammonia is used in the form of aqueous ammonia or ammonia gas or ammonia saturated in an organic solvent. |
