312625-46-0Relevant articles and documents
Efficient enantioselective synthesis of the NMDA 2B receptor antagonist Ro 67-8867
Scalone, Michelangelo,Waldmeier, Pius
, p. 418 - 425 (2013/09/06)
An efficient, enantioselective, and scalable eight-step synthesis for the NMDA 2B receptor antagonist Ro 67-8867 (S,S)-1 selected for the treatment of acute ischemie stroke is described based on the coupling reaction of the amino alcohol (S,S)-6 with the sulfone building block 7. The synthesis of the amino alcohol (S,S)-6 was achieved by the highly selective asymmetric hydrogenation of the piperidinone 4*HCl proceeding with concomitant dynamic kinetic resolution to (S,S)-5. Subsequent debenzylation afforded the enantiomerically pure amino alcohol (S,S)-6 after ee-enhancement by simple crystallization in good yield. The hydrogenation substrate 4*HCl was prepared as a stable hydrochloride in two steps from ethyl N-benzyl-3-oxo-4-piperidinecarboxylate hydrochloride (2) for which a new, short, efficient, and cheap synthesis was developed. To bypass a mutagenic intermediate, a revised safe protocol for the sulfone building block 7 was established. The new synthesis allows the access to Ro 67-8867 (S,S)-1 in an overall yield of 53% compared to 3.5% of the Discovery Chemistry approach.
Ethanesulfonyl-piperidine derivatives
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, (2008/06/13)
The invention relates to compounds of the general formula STR1whereinR 1 signifies hydrogen or hydroxy; R 2 signifies hydrogen or methyl; and X signifies --O-- or --CH 2 -- and their pharmaceutically acceptable acid addition salts.It has been shown that these compounds have a good affitity to the NMDA receptor and they are therefore useful in the treatment of diseases, wherein the therapeutic indications include acute forms of neurodegeneration caused, e.g., by stroke or brain trauma; chronic forms of neurodegeneration such as Alzheimer''s disease, Parkinson''s disease, Huntington''s disease or ALS (amyotrophic lateral sclerosis); neurodegeneration associated with bacterial or viral infections, and, diseases such as schizophrenia, anxiety, depression and chronic/acute pain.
