CN1611494A - N-[1(s)-乙氧羰基-3-苯丙基] -l-丙氨酸-n-羧酸酐的化学合成方法 - Google Patents
N-[1(s)-乙氧羰基-3-苯丙基] -l-丙氨酸-n-羧酸酐的化学合成方法 Download PDFInfo
- Publication number
- CN1611494A CN1611494A CN 200310108227 CN200310108227A CN1611494A CN 1611494 A CN1611494 A CN 1611494A CN 200310108227 CN200310108227 CN 200310108227 CN 200310108227 A CN200310108227 A CN 200310108227A CN 1611494 A CN1611494 A CN 1611494A
- Authority
- CN
- China
- Prior art keywords
- ala
- hydrocinnamyl
- ethoxycarbonyl
- acid anhydride
- carboxylic acid
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
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- 238000003786 synthesis reaction Methods 0.000 title claims description 20
- 238000000034 method Methods 0.000 title abstract description 6
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims abstract description 33
- 239000003960 organic solvent Substances 0.000 claims abstract description 30
- -1 ester carbonate Chemical class 0.000 claims abstract description 26
- 239000002994 raw material Substances 0.000 claims abstract description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 150000002170 ethers Chemical class 0.000 claims description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 17
- 230000035484 reaction time Effects 0.000 claims description 15
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 150000003254 radicals Chemical class 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 238000010792 warming Methods 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 claims description 4
- MLFHJEHSLIIPHL-UHFFFAOYSA-N isoamyl acetate Chemical compound CC(C)CCOC(C)=O MLFHJEHSLIIPHL-UHFFFAOYSA-N 0.000 claims description 4
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 claims description 4
- PGMYKACGEOXYJE-UHFFFAOYSA-N pentyl acetate Chemical compound CCCCCOC(C)=O PGMYKACGEOXYJE-UHFFFAOYSA-N 0.000 claims description 4
- 229940090181 propyl acetate Drugs 0.000 claims description 4
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 4
- 229960001701 chloroform Drugs 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 claims description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 2
- HFZLSTDPRQSZCQ-UHFFFAOYSA-N 1-pyrrolidin-3-ylpyrrolidine Chemical compound C1CCCN1C1CNCC1 HFZLSTDPRQSZCQ-UHFFFAOYSA-N 0.000 claims description 2
- UHOPWFKONJYLCF-UHFFFAOYSA-N 2-(2-sulfanylethyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCS)C(=O)C2=C1 UHOPWFKONJYLCF-UHFFFAOYSA-N 0.000 claims description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 2
- YEJCDKJIEMIWRQ-UHFFFAOYSA-N Linopirdine Chemical compound O=C1N(C=2C=CC=CC=2)C2=CC=CC=C2C1(CC=1C=CN=CC=1)CC1=CC=NC=C1 YEJCDKJIEMIWRQ-UHFFFAOYSA-N 0.000 claims description 2
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 150000003851 azoles Chemical class 0.000 claims description 2
- 229940043232 butyl acetate Drugs 0.000 claims description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 2
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 229940093499 ethyl acetate Drugs 0.000 claims description 2
- 150000005826 halohydrocarbons Chemical class 0.000 claims description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 2
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 claims description 2
- 229940117955 isoamyl acetate Drugs 0.000 claims description 2
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 claims description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 2
- 229940011051 isopropyl acetate Drugs 0.000 claims description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 2
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 claims description 2
- 150000002576 ketones Chemical class 0.000 claims description 2
- 229940017219 methyl propionate Drugs 0.000 claims description 2
- TWSRVQVEYJNFKQ-UHFFFAOYSA-N pentyl propanoate Chemical compound CCCCCOC(=O)CC TWSRVQVEYJNFKQ-UHFFFAOYSA-N 0.000 claims description 2
- 150000003672 ureas Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 239000003814 drug Substances 0.000 abstract description 3
- 108010061435 Enalapril Proteins 0.000 abstract description 2
- 108010007859 Lisinopril Proteins 0.000 abstract description 2
- 229960000873 enalapril Drugs 0.000 abstract description 2
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 abstract description 2
- 229960002394 lisinopril Drugs 0.000 abstract description 2
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 abstract description 2
- 229960003401 ramipril Drugs 0.000 abstract description 2
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 abstract description 2
- CEIWXEQZZZHLDM-AAEUAGOBSA-N (2s)-2-[[(2s)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoic acid Chemical compound CCOC(=O)[C@@H](N[C@@H](C)C(O)=O)CCC1=CC=CC=C1 CEIWXEQZZZHLDM-AAEUAGOBSA-N 0.000 abstract 1
- 239000003054 catalyst Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 32
- 238000002360 preparation method Methods 0.000 description 31
- 238000005303 weighing Methods 0.000 description 18
- 238000002425 crystallisation Methods 0.000 description 13
- 230000008025 crystallization Effects 0.000 description 13
- SNDGLCYYBKJSOT-UHFFFAOYSA-N 1,1,3,3-tetrabutylurea Chemical group CCCCN(CCCC)C(=O)N(CCCC)CCCC SNDGLCYYBKJSOT-UHFFFAOYSA-N 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- MFGOZCIHXVFZBC-UHFFFAOYSA-N 1-propylpyrrole Chemical compound CCCN1C=CC=C1 MFGOZCIHXVFZBC-UHFFFAOYSA-N 0.000 description 4
- UWHSPZZUAYSGTB-UHFFFAOYSA-N 1,1,3,3-tetraethylurea Chemical compound CCN(CC)C(=O)N(CC)CC UWHSPZZUAYSGTB-UHFFFAOYSA-N 0.000 description 3
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 3
- JZFDVPLHSQESAW-UHFFFAOYSA-N 1,1,3,3-tetrapropylurea Chemical compound CCCN(CCC)C(=O)N(CCC)CCC JZFDVPLHSQESAW-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- IIYSNNBEZBAQCQ-UHFFFAOYSA-N 1-butylpyrrole Chemical class CCCCN1C=CC=C1 IIYSNNBEZBAQCQ-UHFFFAOYSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 1
- MONRWRVYLOHUFA-UHFFFAOYSA-N pentylurea Chemical compound CCCCCNC(N)=O MONRWRVYLOHUFA-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN 200310108227 CN1252056C (zh) | 2003-10-28 | 2003-10-28 | N-〔1(s)-乙氧羰基-3-苯丙基〕-l-丙氨酸-n-羧酸酐的化学合成方法 |
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CN 200310108227 CN1252056C (zh) | 2003-10-28 | 2003-10-28 | N-〔1(s)-乙氧羰基-3-苯丙基〕-l-丙氨酸-n-羧酸酐的化学合成方法 |
Publications (2)
Publication Number | Publication Date |
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CN1611494A true CN1611494A (zh) | 2005-05-04 |
CN1252056C CN1252056C (zh) | 2006-04-19 |
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CN 200310108227 Expired - Lifetime CN1252056C (zh) | 2003-10-28 | 2003-10-28 | N-〔1(s)-乙氧羰基-3-苯丙基〕-l-丙氨酸-n-羧酸酐的化学合成方法 |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102659709A (zh) * | 2012-04-25 | 2012-09-12 | 上海交通大学 | 一种光敏性α-氨基酸-N-羧酸酐及其合成方法 |
CN105294827A (zh) * | 2014-07-21 | 2016-02-03 | 常州制药厂有限公司 | 一种马来酸依那普利的制备方法 |
CN109021064A (zh) * | 2017-06-09 | 2018-12-18 | 扬子江药业集团有限公司 | 一种马来酸依那普利的制备方法 |
-
2003
- 2003-10-28 CN CN 200310108227 patent/CN1252056C/zh not_active Expired - Lifetime
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102659709A (zh) * | 2012-04-25 | 2012-09-12 | 上海交通大学 | 一种光敏性α-氨基酸-N-羧酸酐及其合成方法 |
CN105294827A (zh) * | 2014-07-21 | 2016-02-03 | 常州制药厂有限公司 | 一种马来酸依那普利的制备方法 |
CN109021064A (zh) * | 2017-06-09 | 2018-12-18 | 扬子江药业集团有限公司 | 一种马来酸依那普利的制备方法 |
CN109021064B (zh) * | 2017-06-09 | 2021-11-09 | 扬子江药业集团有限公司 | 一种马来酸依那普利的制备方法 |
Also Published As
Publication number | Publication date |
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CN1252056C (zh) | 2006-04-19 |
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Assignee: ZHEJIANG CHANGMING PHARMACEUTICAL Co.,Ltd. Assignor: Zhejiang University of Technology Contract fulfillment period: 2007.4.18 to 2012.12.31 Contract record no.: 2008330001345 Denomination of invention: Chemical synthesis of N [1 (S) - oxo - 3 - propyl] L alanine N carboxylic acid anhydride Granted publication date: 20060419 License type: Exclusive license Record date: 20081024 |
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Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2007.4.18 TO 2012.12.31; CHANGE OF CONTRACT Name of requester: ZHEJIANG PROVINCE CHANGMING PHARMACEUTICAL CO., LT Effective date: 20081024 |
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