The selection of a commercial route for the D1 antagonist Sch-39166.
D1 Antagonists have been reported to be potentially useful in a number of therapeutic areas. Sch-39166 is an example of such a selective D1 antagonist. Three different routes based on (1S,2S)-1-phenyl-1,3-propanediol (19), (+)-L-homophenylalanine (27) or trans-(+)-(1R,2R)-2-hydroxy-1-(methylamino)-1,2,3,4-tetrahydronaphthalene (37) were developed for the commercial preparation of Sch-39166. After analyzing each route for the best combination of cost, yield, throughput and efficiency, the synthesis of Sch-39166 starting from 37, which involves the opening of an aziridinium, was selected for optimization into the commercial route.
Hou
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Rhodia ChiRex Inc, 383 Phoenixville Pike, Malvem, PA 19355, USA. donald.hou@rhodiachirex.com
Schumacher
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D001552:Benzazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000191:economics; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000191:economics; D004345:Drug Industry / Q000191:economics; D007202:Indicators and Reagents; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*
D001552:Benzazepines; D018492:Dopamine Antagonists; D007202:Indicators and Reagents; D017447:Receptors, Dopamine D1; C058081:ecopipam