Title:
PREPARATION PROCESS FOR AMANTADINE NITRATE DERIVATIVE
Document Type and Number:
WIPO Patent Application WO/2020/052179
Kind Code:
A1
Abstract:
Provided is a preparation process for an amantadine nitrate derivative. The preparation process comprises preparing the amantadine nitrate derivative from substituted or unsubstituted adamantane used as a raw material by means of the following steps: (1) synthesis of adamantanol; (2) carboxylation of adamantanol; (3) amidation of adamantane acid; (4) reduction; (5) hydrolysis of acylamino adamantanol, and Boc protection of amino; (6) crystallization of Boc-protected amantadine alcohol; (7) nitric acid esterification of Boc-protected amantadine alcohol; (8) refinement of a nitric acid esterification product; (9) amino de-protection and salt formation; and (10) refinement of amantadine nitrate. The amantadine nitrate derivative is represented by formula (I), wherein R1 and R2 are same or different, and respectively are hydrogen, straight-chain or branched alkyl, substituted or unsubstituted aryl, and hetero aryl. The preparation process is efficient, economic, green, safe, and reliable, and is suitable for an industrially produced amantadine nitrate derivative.
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Inventors:
WANG YUQIANG (CN)
LIU ZHENG (CN)
SUN YEWEI (CN)
ZHANG ZAIJUN (CN)
ZHANG GAOXIAO (CN)
LIU ZHENG (CN)
SUN YEWEI (CN)
ZHANG ZAIJUN (CN)
ZHANG GAOXIAO (CN)
Application Number:
PCT/CN2019/000178
Publication Date:
March 19, 2020
Filing Date:
September 11, 2019
Export Citation:
Assignee:
QINGDAO HAILAN PHARMACEUTICALS CO LTD (CN)
International Classes:
C07C209/00; C07C209/62; C07C209/84; C07C211/38; C07C231/06; C07C233/06
Domestic Patent References:
| WO2009057140A2 | 2009-05-07 |
Foreign References:
| CN107365255A | 2017-11-21 | |||
| CN105294450A | 2016-02-03 | |||
| CN1486180A | 2004-03-31 | |||
| CN109206317A | 2019-01-15 | |||
| CN105294450A | 2016-02-03 |
Other References:
LIU, ZHENG ET AL.: "Synthesis and Biological Evaluation of Memantine Nitrates as a Potential Treatment for Neurodegenerative Diseases", MEDICAL CHEMESTRY COMMUNICATION, vol. 8, no. 1, 20 October 2016 (2016-10-20), pages 135 - 147, XP055692256, ISSN: 2040-2503, DOI: 10.1039/C6MD00509H
LIPTON ET AL., JOURNAL OF NEUROCHEMISTRY, vol. 97, 2006, pages 1611 - 1626
WENK ET AL., CNS DRUG REVIEWS, vol. 9, no. 3, 2003, pages 275 - 308
MCKEAGE, DRUGS & AGING, vol. 27, no. 2, 2010, pages 177 - 179
LIU ET AL., MED. CHEM. COMM., vol. 8, 2017, pages 135 - 147
See also references of EP 3851433A4
LIPTON ET AL., JOURNAL OF NEUROCHEMISTRY, vol. 97, 2006, pages 1611 - 1626
WENK ET AL., CNS DRUG REVIEWS, vol. 9, no. 3, 2003, pages 275 - 308
MCKEAGE, DRUGS & AGING, vol. 27, no. 2, 2010, pages 177 - 179
LIU ET AL., MED. CHEM. COMM., vol. 8, 2017, pages 135 - 147
See also references of EP 3851433A4
Attorney, Agent or Firm:
PANTERRAIN IP ATTORNEYS (CN)
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