Title:
INDUSTRIAL PROCESS OF MONO-ALKYLATING A PIPERIDINE NITROGEN IN PIPERIDINE DERIVATIVES WITH DEUTERATED-ALKYL
Document Type and Number:
WIPO Patent Application WO/2019/049918
Kind Code:
A1
Abstract:
The present invention relates to a method of mono-alkylating a piperidine nitrogen in a piperidine derivative with a deuterated lower-alkyl, which comprises protecting the piperidine nitrogen with an aralkyl protective group, lower-alkylating the piperidine nitrogen with a deuterated-lower-alkylating agent under neutral or basic condition, and then deprotecting the aralkyl protective group.
Inventors:
NAKAI YUYA (JP)
HAYASHI MASASHI (JP)
MITSUHASHI WATARU (JP)
HAYASHI MASASHI (JP)
MITSUHASHI WATARU (JP)
Application Number:
PCT/JP2018/032983
Publication Date:
March 14, 2019
Filing Date:
September 06, 2018
Export Citation:
Assignee:
OTSUKA PHARMA CO LTD (JP)
International Classes:
C07D221/28; C07B59/00
Domestic Patent References:
| WO2008137474A1 | 2008-11-13 | |||
| WO2018039642A1 | 2018-03-01 | |||
| WO2008137474A1 | 2008-11-13 |
Other References:
IAN FELLOWS ET AL: "Simple methods for the labelling of N-methyl amines using isotopically labelled methyl iodide", JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, JOHN WILEY, GB, vol. 41, no. 12, 1 January 1998 (1998-01-01), pages 1127 - 1143, XP002474309, ISSN: 0362-4803, DOI: 10.1002/(SICI)1099-1344(199812)41:12<1127::AID-JLCR158>3.0.CO;2-9
HEDVIG BÖLCSKEI ET AL: "Synthesis of deuterated dextromethorphan derivatives", ARKIVOC, vol. 3, 1 January 2008 (2008-01-01), pages 182 - 193, XP055518256
HEINKELE G ET AL: "Synthesis of [2H3]-dextromethorphan and its major urinary metabolites [2H3]-dxtrorphan and [2H3]-dextrorphan-beta-glucoronide", JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, JOHN WILEY, GB, vol. 45, 1 January 2002 (2002-01-01), pages 1153 - 1158, XP002490642, ISSN: 0362-4803, DOI: 10.1002/JLCR.640
J LABEL COMPD RADIOPHARM, vol. 45, 2002, pages 1153 - 1158
T. W. GREENE; P. G. M. WUTS: "Greene's Protective Groups in Organic Synthesis", 2006, WILEY
HEDVIG BÖLCSKEI ET AL: "Synthesis of deuterated dextromethorphan derivatives", ARKIVOC, vol. 3, 1 January 2008 (2008-01-01), pages 182 - 193, XP055518256
HEINKELE G ET AL: "Synthesis of [2H3]-dextromethorphan and its major urinary metabolites [2H3]-dxtrorphan and [2H3]-dextrorphan-beta-glucoronide", JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, JOHN WILEY, GB, vol. 45, 1 January 2002 (2002-01-01), pages 1153 - 1158, XP002490642, ISSN: 0362-4803, DOI: 10.1002/JLCR.640
J LABEL COMPD RADIOPHARM, vol. 45, 2002, pages 1153 - 1158
T. W. GREENE; P. G. M. WUTS: "Greene's Protective Groups in Organic Synthesis", 2006, WILEY
Attorney, Agent or Firm:
YAMAO, Norihito et al. (JP)
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