PROCESSES FOR THE PREPARATION OF 5-HT2C RECEPTOR AGONISTS

摘要

The present invention relates to processes and intermediates useful in the preparation of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (lorcaserin), a serotonin (5-HT) receptor modulator that is useful in the treatment of, for example, central nervous system disorders, such as obesity.

主权项

1. A process for preparing a compound selected from: 2-chloro-N-(4-chlorophenethyl)propan-1-amine (Compound VI), which has the following structure: and salts thereof; comprising the following steps: (a) reacting 2-(4-chlorophenyl)ethanol (Compound II): or a salt thereof, with a first chlorinating agent to form 1-chloro-4-(2-chloroethyl)benzene (Compound III): wherein
said reacting 2-(4-chlorophenyl)ethanol or a salt thereof, with said first chlorinating agent, is performed in the presence of a first catalyst, wherein said first catalyst comprises N,N-dimethylacetamide; (b) reacting said 1-chloro-4-(2-chloroethyl)benzene (Compound III) with 1-aminopropan-2-ol (Compound IV): or a salt thereof, to form 1-(4-chlorophenethylamino)propan-2-ol (Compound V): or a salt thereof; and (c) reacting said 1-(4-chlorophenethylamino)propan-2-ol (Compound V) or a salt thereof, with a second chlorinating agent to form said compound selected from: 2-chloro-N-(4-chlorophenethyl)propan-1-amine (Compound VI) and salts thereof,
wherein said reacting said 1-(4-chlorophenethylamino)propan-2-ol (Compound V or a salt thereof, with said second chlorinating agent, comprises formation of a reaction mixture by addition of said 1-(4-chlorophenethylamino)propan-2-ol to said second chlorinating agent.