CN112441975A - 一种罗沙司他重要中间体的制备方法 - Google Patents
一种罗沙司他重要中间体的制备方法 Download PDFInfo
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- CN112441975A CN112441975A CN201910825689.4A CN201910825689A CN112441975A CN 112441975 A CN112441975 A CN 112441975A CN 201910825689 A CN201910825689 A CN 201910825689A CN 112441975 A CN112441975 A CN 112441975A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 26
- 150000001875 compounds Chemical class 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 15
- 239000002904 solvent Substances 0.000 claims abstract description 15
- 239000000852 hydrogen donor Substances 0.000 claims abstract description 14
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims abstract description 13
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000007868 Raney catalyst Substances 0.000 claims abstract description 7
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910000564 Raney nickel Inorganic materials 0.000 claims abstract description 7
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims abstract description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims abstract description 6
- 235000019253 formic acid Nutrition 0.000 claims abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 150000001412 amines Chemical group 0.000 claims description 2
- 238000002844 melting Methods 0.000 claims description 2
- 230000008018 melting Effects 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- QXTIBZLKQPJVII-UHFFFAOYSA-N triethylsilicon Chemical compound CC[Si](CC)CC QXTIBZLKQPJVII-UHFFFAOYSA-N 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 abstract description 6
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 abstract description 3
- 239000012450 pharmaceutical intermediate Substances 0.000 abstract description 2
- 230000003321 amplification Effects 0.000 abstract 1
- 238000003199 nucleic acid amplification method Methods 0.000 abstract 1
- 238000001914 filtration Methods 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- 238000004537 pulping Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- DOUMFZQKYFQNTF-WUTVXBCWSA-N (R)-rosmarinic acid Chemical compound C([C@H](C(=O)O)OC(=O)\C=C\C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 DOUMFZQKYFQNTF-WUTVXBCWSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101710138860 Hypoxia-inducible factor prolyl hydroxylase Proteins 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- RUOKEQAAGRXIBM-GFCCVEGCSA-N rasagiline Chemical compound C1=CC=C2[C@H](NCC#C)CCC2=C1 RUOKEQAAGRXIBM-GFCCVEGCSA-N 0.000 description 2
- 229960000245 rasagiline Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XJOTXKZIRSHZQV-RXHOOSIZSA-N (3S)-3-amino-4-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S,3S)-1-[[(1R,6R,12R,17R,20S,23S,26R,31R,34R,39R,42S,45S,48S,51S,59S)-51-(4-aminobutyl)-31-[[(2S)-6-amino-1-[[(1S,2R)-1-carboxy-2-hydroxypropyl]amino]-1-oxohexan-2-yl]carbamoyl]-20-benzyl-23-[(2S)-butan-2-yl]-45-(3-carbamimidamidopropyl)-48-(hydroxymethyl)-42-(1H-imidazol-4-ylmethyl)-59-(2-methylsulfanylethyl)-7,10,19,22,25,33,40,43,46,49,52,54,57,60,63,64-hexadecaoxo-3,4,14,15,28,29,36,37-octathia-8,11,18,21,24,32,41,44,47,50,53,55,58,61,62,65-hexadecazatetracyclo[32.19.8.26,17.212,39]pentahexacontan-26-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-oxobutanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)[C@@H](C)O)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@@H]4CSSC[C@H](NC(=O)[C@H](Cc5ccccc5)NC(=O)[C@@H](NC1=O)[C@@H](C)CC)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1cnc[nH]1)NC3=O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N2)C(=O)NCC(=O)N4)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XJOTXKZIRSHZQV-RXHOOSIZSA-N 0.000 description 1
- -1 4-hydroxy-1-methyl-7-phenoxy-3-isoquinolyl Chemical group 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010058116 Nephrogenic anaemia Diseases 0.000 description 1
- ZZAFFYPNLYCDEP-HNNXBMFYSA-N Rosmarinsaeure Natural products OC(=O)[C@H](Cc1cccc(O)c1O)OC(=O)C=Cc2ccc(O)c(O)c2 ZZAFFYPNLYCDEP-HNNXBMFYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000010437 erythropoiesis Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 102000018511 hepcidin Human genes 0.000 description 1
- 229940066919 hepcidin Drugs 0.000 description 1
- 108060003558 hepcidin Proteins 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940042040 innovative drug Drugs 0.000 description 1
- 230000010438 iron metabolism Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- DOUMFZQKYFQNTF-MRXNPFEDSA-N rosemarinic acid Natural products C([C@H](C(=O)O)OC(=O)C=CC=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 DOUMFZQKYFQNTF-MRXNPFEDSA-N 0.000 description 1
- TVHVQJFBWRLYOD-UHFFFAOYSA-N rosmarinic acid Natural products OC(=O)C(Cc1ccc(O)c(O)c1)OC(=Cc2ccc(O)c(O)c2)C=O TVHVQJFBWRLYOD-UHFFFAOYSA-N 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (10)
Priority Applications (1)
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CN201910825689.4A CN112441975B (zh) | 2019-09-03 | 2019-09-03 | 一种罗沙司他重要中间体的制备方法 |
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CN201910825689.4A CN112441975B (zh) | 2019-09-03 | 2019-09-03 | 一种罗沙司他重要中间体的制备方法 |
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CN112441975A true CN112441975A (zh) | 2021-03-05 |
CN112441975B CN112441975B (zh) | 2023-10-31 |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115124467A (zh) * | 2022-07-11 | 2022-09-30 | 天津力生制药股份有限公司 | 一种罗沙司他关键中间体的制备方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103435546A (zh) * | 2012-07-16 | 2013-12-11 | 菲布罗根有限公司 | 制备异喹啉化合物的方法 |
CN108017583A (zh) * | 2016-11-01 | 2018-05-11 | 徐州万邦金桥制药有限公司 | 一种可博美的制备方法 |
-
2019
- 2019-09-03 CN CN201910825689.4A patent/CN112441975B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103435546A (zh) * | 2012-07-16 | 2013-12-11 | 菲布罗根有限公司 | 制备异喹啉化合物的方法 |
CN108017583A (zh) * | 2016-11-01 | 2018-05-11 | 徐州万邦金桥制药有限公司 | 一种可博美的制备方法 |
Non-Patent Citations (5)
Title |
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SOREN ROSENDAL JENSEN, ET AL: "APPLICATION OF THE VILSMEIER FORMYLATION IN THE SYNTHESIS OF 11-13C LABELLED IRIDOIDS", 《TETRAHEDRON》, vol. 43, no. 8, 31 December 1987 (1987-12-31), pages 1949 - 1954, XP022057564, DOI: 10.1016/S0040-4020(01)81508-8 * |
刘鹰翔: "药物合成反应", vol. 1, 中国中医药出版社, pages: 258 - 260 * |
化学工业部人事教育司 等: "《有机定量分析》", 30 September 1997, 化学工业出版社, pages: 49 * |
周家成: "甲酸铵及其他甲酸衍生物在药物合成中的应用", 《中国药科大学学报》 * |
周家成: "甲酸铵及其他甲酸衍生物在药物合成中的应用", 《中国药科大学学报》, vol. 20, no. 5, 31 December 1989 (1989-12-31), pages 313 - 320 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115124467A (zh) * | 2022-07-11 | 2022-09-30 | 天津力生制药股份有限公司 | 一种罗沙司他关键中间体的制备方法 |
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Effective date of registration: 20230920 Address after: 850000, No.9 Park South Road, Zone B, Economic and Technological Development Zone, Lhasa City, Tibet Autonomous Region Applicant after: Tibet Jiaxin Jingtian Pharmaceutical Co.,Ltd. Applicant after: NANJING HAIRUN PHARMACEUTICAL Co.,Ltd. Applicant after: JIANGSU AOSAIKANG PHARMACEUTICAL Co.,Ltd. Address before: 210048 No.39, Tankang South Road, Changlu street, Jiangbei new district, Nanjing City, Jiangsu Province Applicant before: NANJING HAIRUN PHARMACEUTICAL Co.,Ltd. Applicant before: JIANGSU AOSAIKANG PHARMACEUTICAL Co.,Ltd. |
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