WO2006064296A1 - Process for the preparation of (e)-n,n-diethyl-2-cyano-3(3,4-dihydroxy-5-nitro-phenyl)-acrylamide in stable polymorphic form and intermediates of the process - Google Patents

Process for the preparation of (e)-n,n-diethyl-2-cyano-3(3,4-dihydroxy-5-nitro-phenyl)-acrylamide in stable polymorphic form and intermediates of the process Download PDF

Info

Publication number: WO2006064296A1
Authority: WO; WIPO (PCT)
Prior art keywords: diethyl; formula; cyano; acrylamide; hydroxy
Prior art date: 2004-12-15

Application number

PCT/HU2005/000131

Other languages

English (en)

French (fr)

Inventor

Zoltan Cziaky

Original Assignee

Alkaloida Kutato Es Fejlesztö Kft

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2004-12-15

Filing date

2005-12-13

Publication date

2006-06-22

2005-12-13 Application filed by Alkaloida Kutato Es Fejlesztö Kft filed Critical Alkaloida Kutato Es Fejlesztö Kft

2006-06-22 Publication of WO2006064296A1 publication Critical patent/WO2006064296A1/en

Links

238000000034 method Methods 0.000 title claims abstract description 31
238000002360 preparation method Methods 0.000 title claims abstract description 16
239000000543 intermediate Substances 0.000 title description 6
JRURYQJSLYLRLN-BJMVGYQFSA-N entacapone Chemical compound CCN(CC)C(=O)C(\C#N)=C\C1=CC(O)=C(O)C([N+]([O-])=O)=C1 JRURYQJSLYLRLN-BJMVGYQFSA-N 0.000 title description 5
150000007524 organic acids Chemical class 0.000 claims abstract description 9
MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 claims abstract description 9
FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 claims abstract description 9
235000012141 vanillin Nutrition 0.000 claims abstract description 9
DBTGDJLRURNRLD-XYOKQWHBSA-N (e)-2-cyano-n,n-diethyl-3-(4-hydroxy-3-methoxyphenyl)prop-2-enamide Chemical compound CCN(CC)C(=O)C(\C#N)=C\C1=CC=C(O)C(OC)=C1 DBTGDJLRURNRLD-XYOKQWHBSA-N 0.000 claims abstract description 7
MAZRYCCTAIVEQP-IZZDOVSWSA-N 3-O-methylentacapone Chemical compound CCN(CC)C(=O)C(\C#N)=C\C1=CC(OC)=C(O)C([N+]([O-])=O)=C1 MAZRYCCTAIVEQP-IZZDOVSWSA-N 0.000 claims abstract description 7
-1 amine compound Chemical class 0.000 claims abstract description 7
239000003054 catalyst Substances 0.000 claims abstract description 7
229940117913 acrylamide Drugs 0.000 claims abstract 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 26
150000001875 compounds Chemical class 0.000 claims description 25
238000006243 chemical reaction Methods 0.000 claims description 9
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 8
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 7
229910017604 nitric acid Inorganic materials 0.000 claims description 7
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
239000000010 aprotic solvent Substances 0.000 claims description 5
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 5
239000002841 Lewis acid Substances 0.000 claims description 4
RYSHIRFTLKZVIH-UHFFFAOYSA-N N,N-diethylcyanoacetamide Chemical compound CCN(CC)C(=O)CC#N RYSHIRFTLKZVIH-UHFFFAOYSA-N 0.000 claims description 4
150000007517 lewis acids Chemical class 0.000 claims description 4
150000007530 organic bases Chemical class 0.000 claims description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 3
150000003335 secondary amines Chemical class 0.000 claims description 3
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
150000007933 aliphatic carboxylic acids Chemical class 0.000 claims description 2
239000012736 aqueous medium Substances 0.000 claims description 2
229940113088 dimethylacetamide Drugs 0.000 claims description 2
238000006396 nitration reaction Methods 0.000 claims description 2
JRURYQJSLYLRLN-UHFFFAOYSA-N 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-propenamide Chemical compound CCN(CC)C(=O)C(C#N)=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 JRURYQJSLYLRLN-UHFFFAOYSA-N 0.000 claims 1
239000003377 acid catalyst Substances 0.000 claims 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
239000000047 product Substances 0.000 description 15
238000001816 cooling Methods 0.000 description 14
239000000203 mixture Substances 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 8
238000004128 high performance liquid chromatography Methods 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
229940074355 nitric acid Drugs 0.000 description 5
229960003337 entacapone Drugs 0.000 description 4
238000000746 purification Methods 0.000 description 4
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
238000002441 X-ray diffraction Methods 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
238000009835 boiling Methods 0.000 description 3
230000017858 demethylation Effects 0.000 description 3
238000010520 demethylation reaction Methods 0.000 description 3
229910000042 hydrogen bromide Inorganic materials 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
230000035484 reaction time Effects 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000002253 acid Substances 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
238000001914 filtration Methods 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000000725 suspension Substances 0.000 description 2
RNQBKZQLNUBWCE-UHFFFAOYSA-N 2-cyano-n,n-diethylacetamide;hydrochloride Chemical compound Cl.CCN(CC)C(=O)CC#N RNQBKZQLNUBWCE-UHFFFAOYSA-N 0.000 description 1
BBFJODMCHICIAA-UHFFFAOYSA-N 3,4-dihydroxy-5-nitrobenzaldehyde Chemical compound OC1=CC(C=O)=CC([N+]([O-])=O)=C1O BBFJODMCHICIAA-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
ZEHYRTJBFMZHCY-UHFFFAOYSA-N 5-nitrovanillin Chemical compound COC1=CC(C=O)=CC([N+]([O-])=O)=C1O ZEHYRTJBFMZHCY-UHFFFAOYSA-N 0.000 description 1
102000006378 Catechol O-methyltransferase Human genes 0.000 description 1
108020002739 Catechol O-methyltransferase Proteins 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
239000012649 demethylating agent Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
230000000802 nitrating effect Effects 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
RAIYODFGMLZUDF-UHFFFAOYSA-N piperidin-1-ium;acetate Chemical compound CC([O-])=O.C1CC[NH2+]CC1 RAIYODFGMLZUDF-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
239000002904 solvent Substances 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups

PCT/HU2005/000131 2004-12-15 2005-12-13 Process for the preparation of (e)-n,n-diethyl-2-cyano-3(3,4-dihydroxy-5-nitro-phenyl)-acrylamide in stable polymorphic form and intermediates of the process WO2006064296A1 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
HU0402573A HUP0402573A2 (en)	2004-12-15	2004-12-15	Process for producing stable polymorph form of (e)-n,n-diethyl-3-cyano-3-(3,4-dihydroxi-5-nitrophenyl)-acrylamide and the intermediates of the process
HUP0402573		2004-12-15

Publications (1)

Publication Number	Publication Date
WO2006064296A1 true WO2006064296A1 (en)	2006-06-22

Family

ID=89985687

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
PCT/HU2005/000131 WO2006064296A1 (en)	2004-12-15	2005-12-13	Process for the preparation of (e)-n,n-diethyl-2-cyano-3(3,4-dihydroxy-5-nitro-phenyl)-acrylamide in stable polymorphic form and intermediates of the process

Country Status (2)

Country	Link
HU (1)	HUP0402573A2 (ja)
WO (1)	WO2006064296A1 (ja)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2007077572A1 (en) *	2006-01-02	2007-07-12	Actavis Group Ptc Ehf	A process for the preparation of entacapone form-a
WO2008007093A1 (en) *	2006-07-12	2008-01-17	Pliva Hrvatska D.O.O.	Process and product
EP1935873A1 (en)	2006-12-19	2008-06-25	Dipharma Francis S.r.l.	A process for the preparation of entacapone
EP2251323A1 (en)	2009-05-14	2010-11-17	F.I.S. Fabbrica Italiana Sintetici S.p.A.	Method for the purification of entacapone
WO2011008675A2 (en) *	2009-07-15	2011-01-20	Chadeayne Andrew R	Catecholamine compounds, compositions, and formulations, and methods of using the same
WO2013149566A1 (en) *	2012-04-01	2013-10-10	Sunshine Lake Pharma Co., Ltd.	Process for the preparation of entacapone and its intermediate thereof
CN105061259A (zh) *	2015-08-25	2015-11-18	重庆植恩药业有限公司	一种恩他卡朋a型晶的制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5446194A (en) *	1986-11-28	1995-08-29	Orion-Yhtyma Oy	Pharmacologically active catechol derivatives
WO2005063693A1 (en) *	2003-12-29	2005-07-14	Suven Life Sciences Ltd	Improved process for the preparation of entacapone

2004
- 2004-12-15 HU HU0402573A patent/HUP0402573A2/hu unknown
2005
- 2005-12-13 WO PCT/HU2005/000131 patent/WO2006064296A1/en active Application Filing

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5446194A (en) *	1986-11-28	1995-08-29	Orion-Yhtyma Oy	Pharmacologically active catechol derivatives
WO2005063693A1 (en) *	2003-12-29	2005-07-14	Suven Life Sciences Ltd	Improved process for the preparation of entacapone

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
WIKBERG ET AL.: "Identification of Major Metabolites of the Catechol-O-Methyl Transferase Inhibitor Entacapone in Rats and Humans", DRUG METABOLISM AND DISPOSITION , 21(1), 81-92 CODEN: DMDSAI; ISSN: 0090-9556, vol. 21, no. 1, 1993, pages 81 - 92, XP009064899 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2007077572A1 (en) *	2006-01-02	2007-07-12	Actavis Group Ptc Ehf	A process for the preparation of entacapone form-a
WO2008007093A1 (en) *	2006-07-12	2008-01-17	Pliva Hrvatska D.O.O.	Process and product
EP1935873A1 (en)	2006-12-19	2008-06-25	Dipharma Francis S.r.l.	A process for the preparation of entacapone
US7750177B2 (en)	2006-12-19	2010-07-06	Dipharma Francis S.R.L.	Process for the preparation of entacapone
EP2251323A1 (en)	2009-05-14	2010-11-17	F.I.S. Fabbrica Italiana Sintetici S.p.A.	Method for the purification of entacapone
WO2011008675A2 (en) *	2009-07-15	2011-01-20	Chadeayne Andrew R	Catecholamine compounds, compositions, and formulations, and methods of using the same
WO2011008675A3 (en) *	2009-07-15	2011-04-28	Chadeayne Andrew R	Catecholamine compounds, compositions, and formulations, and methods of using the same
WO2013149566A1 (en) *	2012-04-01	2013-10-10	Sunshine Lake Pharma Co., Ltd.	Process for the preparation of entacapone and its intermediate thereof
CN105061259A (zh) *	2015-08-25	2015-11-18	重庆植恩药业有限公司	一种恩他卡朋a型晶的制备方法

Also Published As

Publication number	Publication date
HU0402573D0 (en)	2005-02-28
HUP0402573A2 (en)	2006-07-28

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