| 摘要 |
<p>Disclosed is a process for preparing 2-(cyclohexylmethyl)-N-{ 2-[(2S)-1-methylpyrrolidin-2-yl]ethyl} -1,2,3,4-tetrahydroisoquinoline-7-sulfonamide, or a pharmaceutically acceptable salt thereof, or a solvate or hydrate of a pharmaceutically acceptable salt comprising: a) coupling (-)-2-(2-aminoethyl)-1-methylpyrrolidine with an amine-protected tetrahydroquinoline-7-sulfonyl chloride to give an amine-protected N-{ 2-[(2S)-1-methylpyrrolidin-2-yl]ethyl} -1,2,3,4-tetrahydroisoquinoline-7-sulfonamide; b) deprotecting the amine-protected N-{ 2-[(2S)-1-methylpyrrolidin-2-yl]ethyl} -1,2,3,4-tetrahydroisoquinoline-7-sulfonamide to give N-{ 2-[(2S)-1-methylpyrrolidin-2-yl]ethyl} -1,2,3,4-tetrahydroisoquinoline-7-sulfonamide or a salt thereof; c) reductively aminating N-{ 2-[(2S)-1-methylpyrrolidin-2-yl]ethyl} -1,2,3,4-tetrahydroisoquinoline-7-sulfonamide or a salt thereof with cyclohexanecarboxaldehyde to form 2-(cyclohexylmethyl)-N-{ 2-[(2S)-1-methylpyrrolidin-2-yl]ethyl} -1,2,3,4-tetrahydroisoquinoline-7-sulfonamide; d) optionally reacting 2-(cyclohexylmethyl)-N-{ 2-[(2S)-1-methylpyrrolidin-2-yl]ethyl} -1,2,3,4-tetrahydroisoquinoline-7-sulfonamide, or a hydrate or solvate thereof, with a stoichiometric amount or an excess of a salt-forming acid in a solvent to form a salt or a hydrate or solvate thereof; and e) optionally recrystallizing the product of step d). Also disclosed is a process for preparing 2-(2,2,2-trifluoroacetyl)-N-{ 2-[(2S)-1-methylpyrrolidin-2-yl]ethyl} -1,2,3,4-tetrahydroisoquinoline-7-sulfonamide comprising coupling 2-(2,2,2-trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonyl chloride and (-)-2-(2-aminoethyl)-1-methylpyrrolidine in the presence of a base and in an inert solvent.</p> |
