JP5611244B2 - ニトロオロチン酸を調製するための新規な方法 - Google Patents
ニトロオロチン酸を調製するための新規な方法 Download PDFInfo
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- JP5611244B2 JP5611244B2 JP2011550584A JP2011550584A JP5611244B2 JP 5611244 B2 JP5611244 B2 JP 5611244B2 JP 2011550584 A JP2011550584 A JP 2011550584A JP 2011550584 A JP2011550584 A JP 2011550584A JP 5611244 B2 JP5611244 B2 JP 5611244B2
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- nitric acid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明の目的は、ニトロオロチン酸を製造する現在の方法に関連する問題を克服し、ニトロオロチン酸を調製するための公知の方法を、特に大規模の方法の経済的(収率、費用及び出発物質の入手可能性)及び生態学的(環境の保護)態様の両方に関して改善し、そして方法の安全性(従業員の保護)を高めることである。
本発明の主題は、反応スキーム1に従う、オロチン酸のニトロ化を介する、ニトロオロチン酸を調製するための新規な改善された方法である。
さらに、反応混合物を水でクエンチした後、そのようにして得られた水含有生成物は、予め乾燥させる必要なく次の工程に直接用いることができ、その結果時間と費用を節約できる。非常に高い純度のため、ジピリダモールの合成における続く工程の生成物は単離する必要がない。
ニトロオロチン酸(II)は、反応スキーム1に従うオロチン酸(I)のニトロ化によって製造される。
ニトロオロチン酸(オロチン酸のニトロ化を介して得られる)
50℃未満に冷却しながら、濃硫酸(H2SO4、約98%)420ml(7.68mol)を、65%硝酸(HNO3)169ml(2.56mol)に加えた。次いで、オロチン酸(1.28mol;純度99.64%)200gを分割して加えた。反応混合物を、撹拌下、50〜55℃に3時間加熱した。
ニトロ化が完了した後、反応混合物を周囲温度(約10〜15℃)に放冷し、次いで、30℃未満に冷却しながら水800mlに注いだ。得られた混合物を約0〜10℃に冷却しながら、ゆっくりと撹拌した。沈殿した生成物を濾別し、そして少量の冷水で洗浄し、次いで約50〜60℃で乾燥させた。
収率:230g(90%)、無水の物質に基づく
純度:98.89%(HPLC)
分解点 230℃を超える
MS(ESI):202(MH+)
13C−NMR (500MHz,D2O,ppm):122.6,150.1,151.7,158.3,162.7
Claims (9)
- 濃硫酸及び発煙硝酸ではない濃硝酸の混合物を用いて、40〜80℃の温度でオロチン酸をニトロ化することを特徴とする、ニトロオロチン酸を調製するための方法。
- 硝酸の濃度が、65%であることを特徴とする、請求項1記載の方法。
- ニトロ化が、40〜60℃の温度で実施されることを特徴とする、請求項1又は2記載の方法。
- ニトロ化が、50〜60℃の温度で実施されることを特徴とする、請求項3記載の方法。
- 硫酸及び硝酸の間のモル比が、1:1から6:1の間であることを特徴とする、請求項1〜4のいずれか一項記載の方法。
- 硫酸及び硝酸の間のモル比が、3:1であることを特徴とする、請求項5記載の方法。
- オロチン酸を、硫酸及び硝酸の混合物に分割して加えることを特徴とする、請求項1〜6のいずれか一項記載の方法。
- 反応混合物が、エタノールを全く含まないことを特徴とする、請求項1〜7のいずれか一項記載の方法。
- 大規模の工業生産のための、請求項1〜8のいずれか一項記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN200910007568A CN101812023A (zh) | 2009-02-23 | 2009-02-23 | 制备硝基乳清酸的新方法 |
CN200910007568.5 | 2009-02-23 | ||
PCT/EP2010/052188 WO2010094791A1 (en) | 2009-02-23 | 2010-02-22 | New process for the preparation of nitroorotic acid |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2012518620A JP2012518620A (ja) | 2012-08-16 |
JP5611244B2 true JP5611244B2 (ja) | 2014-10-22 |
Family
ID=42125911
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011550584A Active JP5611244B2 (ja) | 2009-02-23 | 2010-02-22 | ニトロオロチン酸を調製するための新規な方法 |
Country Status (8)
Country | Link |
---|---|
US (2) | US8513413B2 (ja) |
EP (1) | EP2398779B1 (ja) |
JP (1) | JP5611244B2 (ja) |
CN (3) | CN101812023A (ja) |
DK (1) | DK2398779T3 (ja) |
ES (1) | ES2444519T3 (ja) |
PL (1) | PL2398779T3 (ja) |
WO (1) | WO2010094791A1 (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102702114B (zh) * | 2012-05-28 | 2014-12-17 | 浙江海正化工股份有限公司 | 一种硝基乳清酸的制备方法 |
CN110452180A (zh) * | 2019-06-25 | 2019-11-15 | 南京普锐达医药科技有限公司 | 一种合成2-氯-5-氨基-6-嘧啶甲酸乙酯的方法 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CH592636A5 (ja) | 1975-01-13 | 1977-10-31 | Lonza Ag | |
DD126811B1 (de) * | 1976-07-29 | 1980-12-24 | Herbert Goldner | Verfahren zur herstellung von 5-nitrouracilcarbonsaure-(4) |
-
2009
- 2009-02-23 CN CN200910007568A patent/CN101812023A/zh active Pending
-
2010
- 2010-02-22 US US13/201,486 patent/US8513413B2/en active Active
- 2010-02-22 DK DK10711860.6T patent/DK2398779T3/da active
- 2010-02-22 PL PL10711860T patent/PL2398779T3/pl unknown
- 2010-02-22 CN CN201080006911.5A patent/CN102307864B/zh not_active Expired - Fee Related
- 2010-02-22 ES ES10711860.6T patent/ES2444519T3/es active Active
- 2010-02-22 CN CN201410257632.6A patent/CN104098576B/zh not_active Expired - Fee Related
- 2010-02-22 EP EP10711860.6A patent/EP2398779B1/en active Active
- 2010-02-22 JP JP2011550584A patent/JP5611244B2/ja active Active
- 2010-02-22 WO PCT/EP2010/052188 patent/WO2010094791A1/en active Application Filing
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2013
- 2013-07-18 US US13/945,011 patent/US20130303760A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
CN104098576B (zh) | 2016-03-30 |
EP2398779A1 (en) | 2011-12-28 |
DK2398779T3 (da) | 2014-02-10 |
ES2444519T3 (es) | 2014-02-25 |
EP2398779B1 (en) | 2013-12-18 |
PL2398779T3 (pl) | 2014-05-30 |
US20120123118A1 (en) | 2012-05-17 |
WO2010094791A1 (en) | 2010-08-26 |
CN101812023A (zh) | 2010-08-25 |
US20130303760A1 (en) | 2013-11-14 |
CN104098576A (zh) | 2014-10-15 |
US8513413B2 (en) | 2013-08-20 |
JP2012518620A (ja) | 2012-08-16 |
CN102307864B (zh) | 2014-07-09 |
CN102307864A (zh) | 2012-01-04 |
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