OPTICALLY ACTIVE INTERMEDIATES FOR THE PREPARATION OF OPTICALLY ACTIVE SUBSTITUTED OXIMES, HYDRAZONES AND OLEFINS USEFUL AS NEUROKININ ANTAGONISTS

• Main Authors: TANG, SUHAN, SUDHAKAR, ANANTHA R
• Format: Patent
• Language: English; French
• Published: 06.05.1999
• Edition: 6
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; APPARATUS THEREFOR; CHEMISTRY; CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION ORPROCESSING OF GOODS; GENERAL METHODS OF ORGANIC CHEMISTRY; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS; TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINSTCLIMATE CHANGE

Intermediates having formulas (A) and (B) wherein BI is -CH2OH or -CH2ORP, and RP is an alcohol protecting group; a is 1, 2, or 3; TI is -OH or (C); QI is phenyl, naphthyl or heteroaryl having 1-3 substituents; Ra and Rc are the same, and are H, or are selected from alkyl, cycloalkyl and aryl groups, the groups being optionally substituted with one or more substituents selected from alkyl, cycloalkyl, aryl, or -OH; or Ra and Rc together with the C-N-C chain to which they are bound, form a 5-7 membered ring; Rb and Rd are the same, and are H, or are selected from alkyl, cycloalkyl and aryl groups, the groups being optionally substituted with one or more substituents selected from alkyl, cycloalkyl, aryl, or -OH; and D is a directing group capable of directing lithiation alpha to a nitrogen atom of a nitrogen compound having D as a substituent bound to the nitrogen atom when the nitrogen compound is reacted with s-butyl lithium, are disclosed. The intermediates have an enantiomeric excess of the R enantiomer over the corresponding S enantiomer of greater than 85 %, preferably, greater than 95 %, and are useful for preparing optically active substituted oximes, hydrazones and olefins that are useful as neurokinin antagonists.