- Process development and scale-up of a β-secretase inhibitor via a stereospecific jocic reaction
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A scalable process for the synthesis of a spiropiperidine β-secretase inhibitor is described. Key stereochemical transformations utilized are a diastereoselective trichloromethyl addition followed by an unprecedented stereospecific Jocic reaction with an aniline nucleophile. Simplified processing was developed for a Dieckmann cyclization/decarboxylation sequence to give a process suitable for the production of kilogram quantities of API.
- Henegar, Kevin E.,Lira, Ricardo,Kim, Hui,Gonzalez-Hernandez, Juan
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p. 985 - 990
(2013/08/23)
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- Novel Sultam Compounds
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Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
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Paragraph 0247
(2013/06/27)
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- LACTAMS AS BETA SECRETASE INHIBITORS
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Compound and pharmaceutically acceptable salts of the compound are disclosed, wherein the compound has the structure (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermedia
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Page/Page column 26-27
(2013/02/28)
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- One-pot in situ formation and reaction of trimethyl(trichloromethyl)silane: Application to the synthesis of 2,2,2-trichloromethylcarbinols
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2,2,2-Trichloromethylcarbinols are 1 are valuable synthetic intermediates with a multitude of uses. A scalable procedure for the synthesis of TMS-protected-2,2,2-trichloromethylcarbinols and 2,2,2-trichloromethylcarbinols 1 was developed that employs the in situ generation and reaction of trimethyl(trichloromethyl)silane (CCl3-TMS). The procedure avoids the exposure of the carbonyl compounds to the strongly basic conditions typically used for this transformation and also avoids isolation of the difficult-to-handle CCl3-TMS. This procedure was applied to diastereoselective trichloromethyl additions to 2-substituted 4-piperidinones and to reactions with a variety of structurally diverse aldehydes and ketones.
- Henegar, Kevin E.,Lira, Ricardo
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experimental part
p. 2999 - 3004
(2012/05/04)
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- LACTAMS AS BETA SECRETASE INHIBITORS
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Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment methods of synthesis,
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Page/Page column 64-65
(2010/07/10)
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