UA79991C2 - Process for the industrial synthesis of 5-amino-3-carboxymethyl-4-cyano-2-thiophenecarboxydimethylester and use thereof - Google Patents
Process for the industrial synthesis of 5-amino-3-carboxymethyl-4-cyano-2-thiophenecarboxydimethylester and use thereof Download PDFInfo
- Publication number
- UA79991C2 UA79991C2 UAA200503859A UA2005003859A UA79991C2 UA 79991 C2 UA79991 C2 UA 79991C2 UA A200503859 A UAA200503859 A UA A200503859A UA 2005003859 A UA2005003859 A UA 2005003859A UA 79991 C2 UA79991 C2 UA 79991C2
- Authority
- UA
- Ukraine
- Prior art keywords
- formula
- compound
- synthesis
- reaction
- cyano
- Prior art date
Links
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 17
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 16
- 238000000034 method Methods 0.000 title claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 26
- ZHEZAQJNZMLYBA-UHFFFAOYSA-J distrontium;5-[bis(carboxylatomethyl)amino]-3-(carboxylatomethyl)-4-cyanothiophene-2-carboxylate;octahydrate Chemical compound O.O.O.O.O.O.O.O.[Sr+2].[Sr+2].[O-]C(=O)CN(CC([O-])=O)C=1SC(C([O-])=O)=C(CC([O-])=O)C=1C#N ZHEZAQJNZMLYBA-UHFFFAOYSA-J 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 229940079488 strontium ranelate Drugs 0.000 claims abstract description 8
- DJSXNILVACEBLP-UHFFFAOYSA-N ranelic acid Chemical class OC(=O)CN(CC(O)=O)C=1SC(C(O)=O)=C(CC(O)=O)C=1C#N DJSXNILVACEBLP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229950003464 ranelic acid Drugs 0.000 claims abstract description 7
- 150000004677 hydrates Chemical class 0.000 claims abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 238000010992 reflux Methods 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 239000011593 sulfur Substances 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- -1 Methyl diester Chemical class 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 4
- 239000011541 reaction mixture Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 3
- KNPBNTMMZCNVIE-UHFFFAOYSA-N 5-amino-3-(carboxymethyl)-4-cyanothiophene-2-carboxylic acid Chemical compound NC=1SC(C(O)=O)=C(CC(O)=O)C=1C#N KNPBNTMMZCNVIE-UHFFFAOYSA-N 0.000 claims description 2
- 238000001556 precipitation Methods 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000001308 synthesis method Methods 0.000 claims 2
- 241000080590 Niso Species 0.000 claims 1
- 239000000654 additive Substances 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- IXLRCPSVPMSMMM-UHFFFAOYSA-N methyl 3-(dicyanomethylidene)-5-hydroxy-5-methoxypent-4-enoate Chemical compound COC(=O)CC(=C(C#N)C#N)C=C(O)OC IXLRCPSVPMSMMM-UHFFFAOYSA-N 0.000 claims 1
- 238000012876 topography Methods 0.000 claims 1
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- BLYLWUDQKYBGJD-UHFFFAOYSA-N methyl 5-amino-4-cyano-3-(2-methoxy-2-oxoethyl)thiophene-2-carboxylate Chemical compound COC(=O)CC1=C(C(=O)OC)SC(N)=C1C#N BLYLWUDQKYBGJD-UHFFFAOYSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 229910052712 strontium Inorganic materials 0.000 description 4
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 4
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 159000000003 magnesium salts Chemical class 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 1
- RNJOKCPFLQMDEC-UHFFFAOYSA-N 4(R),8-dimethyl-trans-2-nonenoyl-CoA Chemical compound COC(=O)CC(=O)CC(=O)OC RNJOKCPFLQMDEC-UHFFFAOYSA-N 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical group [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003262 anti-osteoporosis Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229910052749 magnesium Chemical group 0.000 description 1
- 239000011777 magnesium Chemical group 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/23—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and carboxyl groups, other than cyano groups, bound to the same unsaturated acyclic carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0211764A FR2844796A1 (fr) | 2002-09-24 | 2002-09-24 | Nouveau procede de synthese industrielle du diester methylique de l'acide 5-amino-3-carboxymethyl-4-cyano-2- thiophenecarboxylique, et application a la synthese des sels bivalents de l'acide ranelique et de leurs hydrates |
| PCT/FR2003/002776 WO2004029035A1 (fr) | 2002-09-24 | 2003-09-22 | Nouveau procede de synthese industriel du diester methylique de l'acide 5-amino-3-carboxymethyl-4-cyano-2-thiophenecarboxylique, et application a la synthese des sels bivalents de l'acide ranelique et de leurs hydrates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA79991C2 true UA79991C2 (en) | 2007-08-10 |
Family
ID=29415190
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UAA200503859A UA79991C2 (en) | 2002-09-24 | 2003-09-22 | Process for the industrial synthesis of 5-amino-3-carboxymethyl-4-cyano-2-thiophenecarboxydimethylester and use thereof |
Country Status (39)
| Country | Link |
|---|---|
| US (3) | US7105683B2 (is) |
| EP (1) | EP1403264B1 (is) |
| JP (1) | JP4136865B2 (is) |
| KR (1) | KR100551503B1 (is) |
| CN (2) | CN100393707C (is) |
| AP (1) | AP1942A (is) |
| AR (1) | AR041356A1 (is) |
| AT (1) | ATE286041T1 (is) |
| AU (2) | AU2003282178A1 (is) |
| BR (1) | BR0304194A (is) |
| CA (1) | CA2442875C (is) |
| DE (1) | DE60300252T2 (is) |
| DK (1) | DK1403264T3 (is) |
| EA (1) | EA007496B1 (is) |
| EC (1) | ECSP055742A (is) |
| ES (1) | ES2235144T3 (is) |
| FR (1) | FR2844796A1 (is) |
| GE (1) | GEP20074140B (is) |
| HK (2) | HK1061845A1 (is) |
| HR (1) | HRP20050360B1 (is) |
| IL (1) | IL167314A (is) |
| IS (1) | IS2136B (is) |
| MA (1) | MA26101A1 (is) |
| ME (1) | ME00451B (is) |
| MX (1) | MXPA03008645A (is) |
| MY (1) | MY131939A (is) |
| NI (1) | NI200500065A (is) |
| NO (1) | NO328697B1 (is) |
| NZ (1) | NZ528400A (is) |
| OA (1) | OA12933A (is) |
| PL (1) | PL214414B1 (is) |
| PT (1) | PT1403264E (is) |
| RS (1) | RS50929B (is) |
| SG (1) | SG110070A1 (is) |
| SI (1) | SI1403264T1 (is) |
| TN (1) | TNSN05089A1 (is) |
| UA (1) | UA79991C2 (is) |
| WO (1) | WO2004029035A1 (is) |
| ZA (1) | ZA200307410B (is) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2844796A1 (fr) * | 2002-09-24 | 2004-03-26 | Servier Lab | Nouveau procede de synthese industrielle du diester methylique de l'acide 5-amino-3-carboxymethyl-4-cyano-2- thiophenecarboxylique, et application a la synthese des sels bivalents de l'acide ranelique et de leurs hydrates |
| FR2844795B1 (fr) * | 2002-09-24 | 2004-10-22 | Servier Lab | Nouveau procede de synthese industriel du ranelate de strontium et de ses hydrates |
| PL1745791T3 (pl) * | 2003-05-07 | 2013-11-29 | Osteologix As | Leczenie chorób chrząstki/kości za pomocą rozpuszczalnych w wodzie soli strontu |
| EP2266584B1 (en) * | 2003-05-07 | 2012-09-05 | Osteologix A/S | Composition with strontium and vitamin D for the prophylaxis and/or treatment of cartilage and/or bone conditions |
| US20050085531A1 (en) * | 2003-10-03 | 2005-04-21 | Hodge Carl N. | Thiophene-based compounds exhibiting ATP-utilizing enzyme inhibitory activity, and compositions, and uses thereof |
| EP1732575B1 (en) | 2004-02-26 | 2010-12-29 | Osteologix A/S | Strontium-containing compounds for use in the prevention or treatment of necrotic bone conditions |
| ATE443541T1 (de) | 2004-06-25 | 2009-10-15 | Strontin Aps | Zusammensetzungen mit strontium und vitamin d und ihre verwendungen |
| FR2875807B1 (fr) * | 2004-09-30 | 2006-11-17 | Servier Lab | Forme cristalline alpha du ranelate de strontium, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
| US20070292529A1 (en) * | 2006-06-19 | 2007-12-20 | Tabbiner Philip S | Strontium compositions and methods of treating osteoporotic conditions |
| CN101665483B (zh) * | 2008-09-01 | 2013-01-23 | 河北医科大学 | 一种雷尼酸锶中间体化合物ⅱ的合成方法 |
| WO2011110597A1 (de) | 2010-03-11 | 2011-09-15 | Azad Pharmaceutical Ingredients Ag | Verfahren zur herstellung von strontiumranelat |
| CN103319454B (zh) * | 2013-06-14 | 2014-06-18 | 广东众生药业股份有限公司 | 一种高纯度雷尼酸四乙酯及其中间体的制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR415850A (fr) | 1909-07-22 | 1910-10-05 | Gustave Auguste Ferrie | Dispositif de mesure permettant de lire directement la valeur d'une grandeur fonction de deux variables |
| FR2651497B1 (fr) * | 1989-09-01 | 1991-10-25 | Adir | Nouveaux sels de metaux bivalents de l'acide n, n-di (carboxymethyl)amino-2 cyano-3 carboxymethyl-4 carboxy-5 thiophene, leur procede de preparation et les compositions pharmaceutiques les renfermant. |
| FR2844796A1 (fr) * | 2002-09-24 | 2004-03-26 | Servier Lab | Nouveau procede de synthese industrielle du diester methylique de l'acide 5-amino-3-carboxymethyl-4-cyano-2- thiophenecarboxylique, et application a la synthese des sels bivalents de l'acide ranelique et de leurs hydrates |
| FR2844797B1 (fr) * | 2002-09-24 | 2004-10-22 | Servier Lab | Nouveau procede de synthese industriel des tetraesters de l'acide 5-[bis (carboxymethyl)]-3-carboxymethyl-4-cyano-2- thiophenecarboxylique, et application a la synthese des sels bivalents de l'acide ranelique et de leurs hydrates |
-
2002
- 2002-09-24 FR FR0211764A patent/FR2844796A1/fr active Pending
-
2003
- 2003-09-17 MY MYPI20033534A patent/MY131939A/en unknown
- 2003-09-22 AU AU2003282178A patent/AU2003282178A1/en not_active Abandoned
- 2003-09-22 ME MEP-2008-685A patent/ME00451B/me unknown
- 2003-09-22 SI SI200330013T patent/SI1403264T1/xx unknown
- 2003-09-22 DE DE60300252T patent/DE60300252T2/de not_active Expired - Lifetime
- 2003-09-22 AP AP2005003259A patent/AP1942A/xx active
- 2003-09-22 AT AT03292317T patent/ATE286041T1/de active
- 2003-09-22 BR BR0304194-8A patent/BR0304194A/pt not_active Application Discontinuation
- 2003-09-22 PT PT03292317T patent/PT1403264E/pt unknown
- 2003-09-22 OA OA1200500082A patent/OA12933A/en unknown
- 2003-09-22 UA UAA200503859A patent/UA79991C2/uk unknown
- 2003-09-22 RS YUP-2005/0242A patent/RS50929B/sr unknown
- 2003-09-22 GE GEAP20038760A patent/GEP20074140B/en unknown
- 2003-09-22 ES ES03292317T patent/ES2235144T3/es not_active Expired - Lifetime
- 2003-09-22 AU AU2003248279A patent/AU2003248279B2/en not_active Ceased
- 2003-09-22 JP JP2003330438A patent/JP4136865B2/ja not_active Expired - Fee Related
- 2003-09-22 EP EP03292317A patent/EP1403264B1/fr not_active Expired - Lifetime
- 2003-09-22 WO PCT/FR2003/002776 patent/WO2004029035A1/fr not_active Application Discontinuation
- 2003-09-22 DK DK03292317T patent/DK1403264T3/da active
- 2003-09-23 CA CA002442875A patent/CA2442875C/fr not_active Expired - Fee Related
- 2003-09-23 NO NO20034237A patent/NO328697B1/no not_active IP Right Cessation
- 2003-09-23 NZ NZ528400A patent/NZ528400A/en not_active IP Right Cessation
- 2003-09-23 AR ARP030103454A patent/AR041356A1/es not_active Application Discontinuation
- 2003-09-23 EA EA200300926A patent/EA007496B1/ru not_active IP Right Cessation
- 2003-09-23 ZA ZA200307410A patent/ZA200307410B/xx unknown
- 2003-09-23 PL PL362367A patent/PL214414B1/pl unknown
- 2003-09-23 MX MXPA03008645A patent/MXPA03008645A/es active IP Right Grant
- 2003-09-23 KR KR1020030065785A patent/KR100551503B1/ko not_active IP Right Cessation
- 2003-09-24 CN CNB2006100073351A patent/CN100393707C/zh not_active Expired - Fee Related
- 2003-09-24 US US10/669,738 patent/US7105683B2/en not_active Expired - Fee Related
- 2003-09-24 MA MA27320A patent/MA26101A1/fr unknown
- 2003-09-24 CN CNB031348076A patent/CN1280285C/zh not_active Expired - Fee Related
- 2003-09-24 SG SG200305554A patent/SG110070A1/en unknown
-
2004
- 2004-07-05 HK HK04104808A patent/HK1061845A1/xx not_active IP Right Cessation
-
2005
- 2005-03-08 IL IL167314A patent/IL167314A/en not_active IP Right Cessation
- 2005-03-18 NI NI200500065A patent/NI200500065A/es unknown
- 2005-03-23 TN TNP2005000089A patent/TNSN05089A1/fr unknown
- 2005-04-19 IS IS7808A patent/IS2136B/is unknown
- 2005-04-21 HR HRP20050360AA patent/HRP20050360B1/hr not_active IP Right Cessation
- 2005-04-22 EC EC2005005742A patent/ECSP055742A/es unknown
-
2006
- 2006-02-21 US US11/358,496 patent/US7238815B2/en not_active Expired - Fee Related
- 2006-02-21 US US11/358,034 patent/US7462714B2/en not_active Expired - Fee Related
-
2007
- 2007-02-01 HK HK07101197A patent/HK1096661A1/xx not_active IP Right Cessation
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