The practical synthesis of a uterine relaxant, bis(2-[[(2S)-2-([(2R)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxyethyl)-phenyl]ethyl]amino)-1,2,3,4-tetrahydronaphthalen-7-yl]oxy]-N,N-dimethylacetamide) sulfate (KUR-1246).
The synthetic route for a uterine relaxant, bis(2-[[(2S)-2-([(2R)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxyethyl)-phenyl]ethyl]amino)-1,2,3,4-tetrahydronaphthalen-7-yl]oxy]-N,N-dimethylacetamide) sulfate (KUR-1246), was established by the coupling of optically active components, the bromohydrin 14 and the amine 24. We now describe the practical synthesis of these two optically active components. Bromohydrin 14 was obtained by the asymmetric borane reduction of the prochiral phenacyl bromide 13 using a catalyst prepared from aluminum triethoxide and a chiral amino alcohol. The other optically active component 24 was prepared from (S)-AMT.
Yanagi
T
T
Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., Minamiazumi, Nagano, Japan. takashi_yanagi@pharm.kissei.co.jp
Kikuchi
K
K
Takeuchi
H
H
Ishikawa
T
T
Nishimura
T
T
Yamamoto
I
I
D000081:Acetamides / Q000138:chemical synthesis* / Q000494:pharmacology; D000438:Alcohols / Q000138:chemical synthesis / Q000494:pharmacology; D000588:Amines / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D005260:Female; D009215:Myometrium / Q000187:drug effects / Q000502:physiology; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology; D010276:Parasympatholytics / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology
D000081:Acetamides; D000438:Alcohols; D000588:Amines; D009281:Naphthalenes; D010276:Parasympatholytics; C023963:bromohydrins; C425888:bedoradrine