Title:
METHOD FOR PRODUCING MORPHINAN DERIVATIVE
Document Type and Number:
WIPO Patent Application WO/2021/015108
Kind Code:
A1
Abstract:
Provided is a method for producing a morphinan derivative represented by general formula (II), etc., by causing metallic sodium and ethylenediamine to act on a morphinan derivative represented by general formula (I) in the presence of an auxiliary solvent. (In the formula, R1 represents a hydrogen atom or an optionally substituted C1-10 alkyl group, C3-6 cycloalkyl group, C2-6 alkenyl group, C6-10 aryl group or heteroaryl group, R2 represents an amino protecting group, R3 represents a methoxy group, R4 and R5 represent a hydrogen atom or a hydroxy group, R6 and R7 represent a hydrogen atom or an electron-donating group; here, R6 and R7 are not simultaneously hydrogen atoms, and X represents O or CH2.)
Inventors:
SAITO DAISUKE (JP)
HAYASHIDA KOHEI (JP)
HAYASHIDA KOHEI (JP)
Application Number:
PCT/JP2020/027767
Publication Date:
January 28, 2021
Filing Date:
July 17, 2020
Export Citation:
Assignee:
NIPPON CHEMIPHAR CO (JP)
International Classes:
C07B35/02; C07D471/08
Domestic Patent References:
| WO2014136305A1 | 2014-09-12 | |||
| WO2013035833A1 | 2013-03-14 | |||
| WO2016148232A1 | 2016-09-22 | |||
| WO2013035833A1 | 2013-03-14 | |||
| WO2016148232A1 | 2016-09-22 |
Foreign References:
| JP2015180605A | 2015-10-15 | |||
| US5504208A | 1996-04-02 | |||
| JP2019134051A | 2019-08-08 | |||
| US5504208A | 1996-04-02 |
Other References:
PIRKLE WILLIAM H. ET AL.: "The Derivation of Hydroaromatic Morphinans and Isomorphinans from Natural Sources", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 30, no. 6, June 1965 (1965-06-01), pages 1769 - 1773, XP055786400
LI FUYING ET AL.: "Synthesis and opioid receptor activity of indolopropellanes", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 19, 2009, pages 4603 - 4606, XP055169332, DOI: 10.1016/j.bmcl.2009.06.093
LI FUYING ET AL.: "Synthesis and SAR Study of Opioid Receptor Ligands: Mono- and Bis-Indolomorphinans", CHEMICAL BIOLOGY & DRUG DESIGN, vol. 74, no. 4, October 2009 (2009-10-01), pages 335 - 342, XP055786403
ZHANG AO ET AL.: "Synthesis and Pharmacological Evaluation of 6,7-Indolo/ Thiazolo-Morphinanss-Further SAR of Levorphanol", JOURNAL OF MEDICINAL CHEMISTRY, vol. 50, no. 11, 1 May 2007 (2007-05-01), pages 2747 - 2751, XP055093411
SAWA Y. K. ET AL.: "Elimination of the 4-hydroxyl group of the alkaloids related to morphine—XI", TETRAHEDRON, vol. 24, no. 20, January 1968 (1968-01-01), pages 6185 - 6196, XP055786411
SELFRIDGE BRANDON R. ET AL.: "Structure-Activity Relationships of (+)- Naltrexone-Inspired Toll-like Receptor 4 (TLR4) Antagonists", JOURNAL OF MEDICINAL CHEMISTRY, vol. 58, no. 12, 2015, pages 5038 - 5052, XP055341920, DOI: 10.1021/acs.jmedchem.5b00426
LINDERS J. T. M. ET AL.: "Diels-Alder reaction of 6-demethoxy-j3- dihydrothebaine with methyl vinyl ketone using microwave heating; preparation and pharmacology of 3-hydroxy-a, a, 17-trimethyl -6 beta,14 beta - ethenomorphinan-7beta -methanol, a novel deoxygenated diprenorphine analogue (chemistry of opium alkaloids, part XX", RECUEIL DES TRAVAUX CHIMIQUES DES PAYS-BAS, vol. 107, no. 6, 1 June 1988 (1988-06-01), pages 449 - 454, XP055786416
REVESZ LASZLO ET AL.: "Design and Synthesis of Novel Opiate Antagonists with LH-Stimulating Properties", HELVETICA CHIMICA ACTA, vol. 73, 1990, pages 326 - 336, XP009060656, DOI: 10.1002/hlca.19900730212
NAGASE HIROSHI ET AL.: "Synthesis of a Stable Iminium Salt and Propel lane Derivatives", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 73, no. 20, 17 October 2008 (2008-10-17), pages 8093 - 8096, XP055093356
WATANABE YOSHIKAZU ET AL.: "Design and synthesis of novel d opioid receptor agonists with an azatricyclodecane skeleton for improving blood-brain barrier penetration", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 27, 2017, pages 3495 - 3498, XP085117770, DOI: 10.1016/j.bmcl.2017.05.072
HAYASHIDA KOHEI ET AL.: "Novel delta opioid receptor agonists with oxazatricyclodecane structure showing potent agonistic activities", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 27, no. 12, 1 June 2017 (2017-06-01), pages 2742 - 2745, XP055786181
SAWA Y. K . ET AL.: "ELIMINATION OF THE 4-HYDROXYL GROUP OF THE ALKALOIDS RELATED TO MORPHINE-IV", TETRAHEDRON, vol. 20, no. 10, January 1964 (1964-01-01), pages 2255 - 2258, XP055786425
JOURNAL OF ORGANIC CHEMISTRY, vol. 30, no. 6, 1965, pages 1769 - 1773
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 19, no. 16, 2009, pages 4603 - 4606
CHEMICAL BIOLOGY & DRUG DESIGN, vol. 74, no. 4, 2009, pages 335 - 342
JOURNAL OF MEDICINAL CHEMISTRY, vol. 50, no. 11, 2007, pages 2747 - 2751
TETRAHEDRON, vol. 24, no. 20, 1968, pages 6185 - 96
JOURNAL OF MEDICINAL CHEMISTRY, vol. 58, no. 12, 2015, pages 5038 - 5052
RECUEIL DES TRAVAUX CHIMIQUES DES PAYS-BAS, vol. 107, no. 6, 1988, pages 449 - 54
HELVETICA CHIMICA ACTA, vol. 73, no. 2, 1990, pages 326 - 36
J. ORG. CHEM., vol. 73, 2008, pages 8093 - 8096
LI FUYING ET AL.: "Synthesis and opioid receptor activity of indolopropellanes", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 19, 2009, pages 4603 - 4606, XP055169332, DOI: 10.1016/j.bmcl.2009.06.093
LI FUYING ET AL.: "Synthesis and SAR Study of Opioid Receptor Ligands: Mono- and Bis-Indolomorphinans", CHEMICAL BIOLOGY & DRUG DESIGN, vol. 74, no. 4, October 2009 (2009-10-01), pages 335 - 342, XP055786403
ZHANG AO ET AL.: "Synthesis and Pharmacological Evaluation of 6,7-Indolo/ Thiazolo-Morphinanss-Further SAR of Levorphanol", JOURNAL OF MEDICINAL CHEMISTRY, vol. 50, no. 11, 1 May 2007 (2007-05-01), pages 2747 - 2751, XP055093411
SAWA Y. K. ET AL.: "Elimination of the 4-hydroxyl group of the alkaloids related to morphine—XI", TETRAHEDRON, vol. 24, no. 20, January 1968 (1968-01-01), pages 6185 - 6196, XP055786411
SELFRIDGE BRANDON R. ET AL.: "Structure-Activity Relationships of (+)- Naltrexone-Inspired Toll-like Receptor 4 (TLR4) Antagonists", JOURNAL OF MEDICINAL CHEMISTRY, vol. 58, no. 12, 2015, pages 5038 - 5052, XP055341920, DOI: 10.1021/acs.jmedchem.5b00426
LINDERS J. T. M. ET AL.: "Diels-Alder reaction of 6-demethoxy-j3- dihydrothebaine with methyl vinyl ketone using microwave heating; preparation and pharmacology of 3-hydroxy-a, a, 17-trimethyl -6 beta,14 beta - ethenomorphinan-7beta -methanol, a novel deoxygenated diprenorphine analogue (chemistry of opium alkaloids, part XX", RECUEIL DES TRAVAUX CHIMIQUES DES PAYS-BAS, vol. 107, no. 6, 1 June 1988 (1988-06-01), pages 449 - 454, XP055786416
REVESZ LASZLO ET AL.: "Design and Synthesis of Novel Opiate Antagonists with LH-Stimulating Properties", HELVETICA CHIMICA ACTA, vol. 73, 1990, pages 326 - 336, XP009060656, DOI: 10.1002/hlca.19900730212
NAGASE HIROSHI ET AL.: "Synthesis of a Stable Iminium Salt and Propel lane Derivatives", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 73, no. 20, 17 October 2008 (2008-10-17), pages 8093 - 8096, XP055093356
WATANABE YOSHIKAZU ET AL.: "Design and synthesis of novel d opioid receptor agonists with an azatricyclodecane skeleton for improving blood-brain barrier penetration", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 27, 2017, pages 3495 - 3498, XP085117770, DOI: 10.1016/j.bmcl.2017.05.072
HAYASHIDA KOHEI ET AL.: "Novel delta opioid receptor agonists with oxazatricyclodecane structure showing potent agonistic activities", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 27, no. 12, 1 June 2017 (2017-06-01), pages 2742 - 2745, XP055786181
SAWA Y. K . ET AL.: "ELIMINATION OF THE 4-HYDROXYL GROUP OF THE ALKALOIDS RELATED TO MORPHINE-IV", TETRAHEDRON, vol. 20, no. 10, January 1964 (1964-01-01), pages 2255 - 2258, XP055786425
JOURNAL OF ORGANIC CHEMISTRY, vol. 30, no. 6, 1965, pages 1769 - 1773
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 19, no. 16, 2009, pages 4603 - 4606
CHEMICAL BIOLOGY & DRUG DESIGN, vol. 74, no. 4, 2009, pages 335 - 342
JOURNAL OF MEDICINAL CHEMISTRY, vol. 50, no. 11, 2007, pages 2747 - 2751
TETRAHEDRON, vol. 24, no. 20, 1968, pages 6185 - 96
JOURNAL OF MEDICINAL CHEMISTRY, vol. 58, no. 12, 2015, pages 5038 - 5052
RECUEIL DES TRAVAUX CHIMIQUES DES PAYS-BAS, vol. 107, no. 6, 1988, pages 449 - 54
HELVETICA CHIMICA ACTA, vol. 73, no. 2, 1990, pages 326 - 36
J. ORG. CHEM., vol. 73, 2008, pages 8093 - 8096
Attorney, Agent or Firm:
TANAI Sumio et al. (JP)
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