Stereochemistry of C-6 nucleophilic displacements on 1,1- difluorocyclopropyldibenzosuberanyl substrates. An improved synthesis of multidrug resistance modulator LY335979 trihydrochloride

Journal of Organic Chemistry

Volumn 69, Issue 22, 2004, Pages 7653-7660

  Barnett, Charles J ^a   Huff, Bret ^a   Kobierski, Michael E ^a   Letourneau, Michael ^a   Wilson, Thomas M ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOLS; ISOMERS; MIXTURES; STEREOCHEMISTRY; THERMODYNAMICS;

BROMINATION; DISPLACEMENT CHEMISTRY;

ORGANIC COMPOUNDS;

1,1 DIFLUOROCYCLOPROPYLDIBENZOSUBERANYL DERIVATIVE; 1,1 DIFLUOROHOMOTROPYLIUM DERIVATIVE; ALCOHOL DERIVATIVE; BENZENE DERIVATIVE; BROMINE DERIVATIVE; CYCLOPROPANE DERIVATIVE; FLUORINE DERIVATIVE; LITHIUM BOROHYDRIDE; LITHIUM DERIVATIVE; MS 073; MULTIDRUG RESISTANCE PROTEIN; PIPERAZINE DERIVATIVE; PYRAZINE DERIVATIVE; PYRAZINIUM DERIVATIVE; PYRIDINE DERIVATIVE; PYRIDINIUM DERIVATIVE; UNCLASSIFIED DRUG; ZOSUQUIDAR;

ARTICLE; BROMINATION; CHEMICAL BOND; CHEMICAL REACTION; CONTROL STRATEGY; CYCLOPROPANATION; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; HALOGENATION; ISOMER; MULTIDRUG RESISTANCE; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; REACTION ANALYSIS; REDUCTION; REGULATORY MECHANISM; REPRODUCIBILITY; SOLVENT EFFECT; STEREOCHEMISTRY; STRUCTURE ANALYSIS; SUBSTITUTION REACTION; TECHNIQUE; THERMODYNAMICS;

COMBINATORIAL CHEMISTRY TECHNIQUES; DIBENZOCYCLOHEPTENES; DRUG RESISTANCE, MULTIPLE; HYDROCARBONS, FLUORINATED; HYDROXAMIC ACIDS; MAGNETIC RESONANCE SPECTROSCOPY; MOLECULAR STRUCTURE; QUINOLINES; STEREOISOMERISM;

EID: 6344246095     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo049051v     Document Type: Article

References (32)

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9. For this article we define the relative stereochemistry in all structures related to 2 as anti on the basis of the relatively opposite positions of the cyclopropyl and C-6 substituent groups with respect to the dibenzocycloheptane ring. Syn refers to the orientation of these groups on the same side of the dibenzocyloheptane ring.
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30. Reaction of 5-hydroxyquinoline with (R)-glycidyl nosylate gave about 2% racemization in our hands as found by chiral HPLC analysis of the crude product. Optical purity was restored, however, by crystallization of the product (3) during isolation. Overall stereochemical outcomes for this reaction were in agreement with the Syntex results.
31. A diatomaceous silica filter aid.
32. D -35.6.