Title:
METHOD FOR PRODUCING MORPHINAN DERIVATIVES
Document Type and Number:
WIPO Patent Application WO/2019/168025
Kind Code:
A1
Abstract:
Provided is a method for producing morphinan derivatives having the buprenorphine skeleton. In the method, compounds represented by formula (III) are obtained using a Diels-Alder condensation reaction between (I) and (II). By introducing an electron-withdrawing protective group (X) onto an amide moiety, the amount of dienophile (II) for the condensation reaction is reduced, polymer impurities from (II) are decreased, and the overall reaction time is reduced, thus improving upon the conventional method. This novel method can be applied to industrial-scale production without isolation of the produced intermediates between the steps from the production of (II) from (V) and R9-NH2 to the production of (IV) from (III) by the deprotection of (X).
Inventors:
HIROSE MASAAKI (JP)
Application Number:
PCT/JP2019/007551
Publication Date:
September 06, 2019
Filing Date:
February 27, 2019
Export Citation:
Assignee:
NIPPON CHEMIPHAR CO (JP)
International Classes:
C07D489/12; C07C271/64
Domestic Patent References:
| WO1998043978A1 | 1998-10-08 | |||
| WO2013035833A1 | 2013-03-14 |
Foreign References:
| EP0177122A2 | 1986-04-09 | |||
| JP2008015422A | 2008-01-24 | |||
| JP2014065863A | 2014-04-17 | |||
| KR20130120172A | 2013-11-04 |
Other References:
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HIE, LIANA ET AL.: "Nickel-Catalyzed Esterification of Aliphatic Amides", ANGEWANDTE CHEMIE , INTERNATIONAL EDITION, vol. 55, no. 48, 2016, pages 15129 - 15132, XP055635528, ISSN: 1433-7851
HONG, KI BUM ET AL.: "On the Nature of Rate Acceleration in the Synthesis and Fragmentation of Triazolines by Bronsted Acid: Secondary Catalysis by Water (Hydronium Triflate", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 130, no. 7, 2008, pages 2323 - 2328, XP055635531, ISSN: 0002-7863
RUAN, PENG-PENG ET AL.: "Synthesis of α,β-Unsaturated Amidines through Gold-Catalyzed Intermolecular Reaction of Azides with Ynamides", JOURNAL OF ORGANIC CHEMISTRY, vol. 82, no. 17, 2017, pages 9119 - 9125, XP055635534, ISSN: 0022-3263
KANG, YOUNG KU ET AL.: "Catalytic enantioselective Diels-Alder reactions of acrylate derivatives in the presence of chiral Binap-palladium complexes", BULLETIN OF THE KOREAN CHEMICAL SOCIETY, vol. 29, no. 11, 2008, pages 2093 - 2094, XP055635535, ISSN: 0253-2964
FUJII, HIDEAKI ET AL.: "Drug design and synthesis of epsilon opioid receptor agonist: 17- (cyclopropylmethyl) -4, 5 a -epoxy-3, 6 beta -dihydroxy-6, 14-endo ethenomorphinan-7 alpha - (N-methy 1-N-phenethy 1) carboxamide (TAN-821) inducing antinociception mediated by putative epsilon opioid receptor", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 12, no. 15, 2004, pages 4133 - 4145, XP008050503, ISSN: 0968-0896, DOI: 10.1016/j.bmc.2004.05.024
"GREENE's Protective Groups in Organic Synthesis", 2014, Hoboken, New Jersey, ISBN: 978-1-118-05748-3, article WUTS, PETER G. M., pages: 1151 - 1181
HIE, LIANA ET AL.: "Nickel-Catalyzed Esterification of Aliphatic Amides", ANGEWANDTE CHEMIE , INTERNATIONAL EDITION, vol. 55, no. 48, 2016, pages 15129 - 15132, XP055635528, ISSN: 1433-7851
HONG, KI BUM ET AL.: "On the Nature of Rate Acceleration in the Synthesis and Fragmentation of Triazolines by Bronsted Acid: Secondary Catalysis by Water (Hydronium Triflate", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 130, no. 7, 2008, pages 2323 - 2328, XP055635531, ISSN: 0002-7863
RUAN, PENG-PENG ET AL.: "Synthesis of α,β-Unsaturated Amidines through Gold-Catalyzed Intermolecular Reaction of Azides with Ynamides", JOURNAL OF ORGANIC CHEMISTRY, vol. 82, no. 17, 2017, pages 9119 - 9125, XP055635534, ISSN: 0022-3263
KANG, YOUNG KU ET AL.: "Catalytic enantioselective Diels-Alder reactions of acrylate derivatives in the presence of chiral Binap-palladium complexes", BULLETIN OF THE KOREAN CHEMICAL SOCIETY, vol. 29, no. 11, 2008, pages 2093 - 2094, XP055635535, ISSN: 0253-2964
FUJII, HIDEAKI ET AL.: "Drug design and synthesis of epsilon opioid receptor agonist: 17- (cyclopropylmethyl) -4, 5 a -epoxy-3, 6 beta -dihydroxy-6, 14-endo ethenomorphinan-7 alpha - (N-methy 1-N-phenethy 1) carboxamide (TAN-821) inducing antinociception mediated by putative epsilon opioid receptor", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 12, no. 15, 2004, pages 4133 - 4145, XP008050503, ISSN: 0968-0896, DOI: 10.1016/j.bmc.2004.05.024
"GREENE's Protective Groups in Organic Synthesis", 2014, Hoboken, New Jersey, ISBN: 978-1-118-05748-3, article WUTS, PETER G. M., pages: 1151 - 1181
Attorney, Agent or Firm:
TANAI Sumio et al. (JP)
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