1,1'-Carbonyldiimidazole → 4-Amino-5-chloro-N-(1-(3-methoxypropyl)piperidin-4-yl)-2,3-dihydrobenzofuran-7-carboxamide hydrate

Participants

Reaction Steps

Reaction under N2 flow. 4-Amino-5-chloro-2,3-dihydro-7-benzofurancarboxylic acid (0.18 mol) was dissolved in tetrahydrofuran (360 ml) and this solution was stirred and cooled to ±3° C. 1,1'-Carbonylbis-1H-imidazole (0.18 mol) was added in one portion and cooling was stopped. The mixture was stirred for 75 minutes (became homogeneous after 30 minutes). A solution of 1-(3-methoxypropyl)-4-piperidinamine (0.18 mol) in tetrahydrofuran (90 ml) was added dropwise (exothermic temperature rise from 23° C. to 27° C.). The reaction mixture was stirred for 24 hours. More 1,1'-Carbonylbis-1H-imidazole (0.0125 mol) was added and the reaction mixture was stirred for 75 minutes. More 1-(3-methoxypropyl)-4-piperidinamine (0.0125 mol) was added (in 10 ml THF). The resulting reaction mixture was stirred for 3 hours at room temperature, then for 2.5 hours at reflux temperature. Then, the mixture was stirred for 13 hours, allowing it to cool to room temperature. The solvent was evaporated. The residue was stirred for 8 hours in water (360 ml) and the precipitate was filtered off, washed with water, then dried (vacuum; 30° C.), yielding 62.9 g (95%) 4-amino-5-chloro-2,3-dihydro-N-[1-(3-methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide monohydrate; mp. 90.7° C. (comp. 2).

Provenance & Evidence