CN102336739A - 一种氯雷他定化合物及其制法 - Google Patents
一种氯雷他定化合物及其制法 Download PDFInfo
- Publication number
- CN102336739A CN102336739A CN 201110197487 CN201110197487A CN102336739A CN 102336739 A CN102336739 A CN 102336739A CN 201110197487 CN201110197487 CN 201110197487 CN 201110197487 A CN201110197487 A CN 201110197487A CN 102336739 A CN102336739 A CN 102336739A
- Authority
- CN
- China
- Prior art keywords
- loratadine
- making
- purified
- virahol
- purity
- 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
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 5
- 229960003088 loratadine Drugs 0.000 title abstract description 9
- -1 Loratadine compound Chemical class 0.000 title abstract 3
- 238000000034 method Methods 0.000 claims abstract description 42
- 229920005989 resin Polymers 0.000 claims abstract description 27
- 239000011347 resin Substances 0.000 claims abstract description 27
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000000243 solution Substances 0.000 claims abstract description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000005406 washing Methods 0.000 claims abstract description 11
- 238000010521 absorption reaction Methods 0.000 claims abstract description 10
- 238000001035 drying Methods 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- 239000008213 purified water Substances 0.000 claims abstract description 8
- 239000012670 alkaline solution Substances 0.000 claims abstract description 5
- 239000000739 antihistaminic agent Substances 0.000 claims abstract description 4
- 239000013078 crystal Substances 0.000 claims abstract description 4
- 238000001816 cooling Methods 0.000 claims abstract description 3
- 238000000746 purification Methods 0.000 claims description 33
- 230000000274 adsorptive effect Effects 0.000 claims description 14
- 239000003463 adsorbent Substances 0.000 claims description 12
- 229920001429 chelating resin Polymers 0.000 claims description 11
- 238000002425 crystallisation Methods 0.000 claims description 10
- 230000008025 crystallization Effects 0.000 claims description 10
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 7
- 238000005352 clarification Methods 0.000 claims description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 4
- 238000005304 joining Methods 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 2
- 235000012538 ammonium bicarbonate Nutrition 0.000 claims description 2
- 239000003610 charcoal Substances 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
- 229940124623 antihistamine drug Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 15
- 230000000694 effects Effects 0.000 abstract description 13
- 238000003756 stirring Methods 0.000 abstract description 11
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 abstract description 6
- 239000003480 eluent Substances 0.000 abstract description 4
- 230000001387 anti-histamine Effects 0.000 abstract description 3
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 abstract 1
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 229910001385 heavy metal Inorganic materials 0.000 abstract 1
- 238000011068 loading method Methods 0.000 abstract 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000000047 product Substances 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-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
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 102000003834 Histamine H1 Receptors Human genes 0.000 description 1
- 108090000110 Histamine H1 Receptors Proteins 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 206010028748 Nasal obstruction Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 206010051496 Rhinalgia Diseases 0.000 description 1
- 208000036284 Rhinitis seasonal Diseases 0.000 description 1
- 238000006434 Ritter amidation reaction Methods 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- 230000023445 activated T cell autonomous cell death Effects 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- PQLFROTZSIMBKR-UHFFFAOYSA-N ethenyl carbonochloridate Chemical compound ClC(=O)OC=C PQLFROTZSIMBKR-UHFFFAOYSA-N 0.000 description 1
- LUBGFMZTGFXIIN-UHFFFAOYSA-N ethyl 4-oxopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(=O)CC1 LUBGFMZTGFXIIN-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000002398 materia medica Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 238000012803 optimization experiment Methods 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 208000017022 seasonal allergic rhinitis Diseases 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000001149 thermolysis Methods 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims (9)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN 201110197487 CN102336739B (zh) | 2011-07-15 | 2011-07-15 | 一种氯雷他定化合物及其制法 |
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CN 201110197487 CN102336739B (zh) | 2011-07-15 | 2011-07-15 | 一种氯雷他定化合物及其制法 |
Publications (2)
Publication Number | Publication Date |
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CN102336739A true CN102336739A (zh) | 2012-02-01 |
CN102336739B CN102336739B (zh) | 2012-09-26 |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015084693A3 (en) * | 2013-12-05 | 2015-10-22 | Merck Sharp & Dohme Corp. | New process for preparing loratadine from a ketone intermediate |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004080997A1 (en) * | 2003-03-13 | 2004-09-23 | Morepen Laboratories Limited | Process for the preparation of loratadine |
WO2006006184A2 (en) * | 2004-07-08 | 2006-01-19 | Morepen Laboratories Limited | A process for the manufacturing of loratadine and its intermediates |
-
2011
- 2011-07-15 CN CN 201110197487 patent/CN102336739B/zh not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004080997A1 (en) * | 2003-03-13 | 2004-09-23 | Morepen Laboratories Limited | Process for the preparation of loratadine |
WO2006006184A2 (en) * | 2004-07-08 | 2006-01-19 | Morepen Laboratories Limited | A process for the manufacturing of loratadine and its intermediates |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015084693A3 (en) * | 2013-12-05 | 2015-10-22 | Merck Sharp & Dohme Corp. | New process for preparing loratadine from a ketone intermediate |
Also Published As
Publication number | Publication date |
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CN102336739B (zh) | 2012-09-26 |
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C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
ASS | Succession or assignment of patent right |
Owner name: HAINAN LINGKANG PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: HAINAN LIONCO PHARMACEUTICAL GROUP CO., LTD. Effective date: 20130926 |
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C41 | Transfer of patent application or patent right or utility model | ||
C56 | Change in the name or address of the patentee |
Owner name: HAINAN LIONCO PHARMACEUTICAL GROUP CO., LTD. Free format text: FORMER NAME: HAINAN LINGKANG PHARMACEUTICAL CO., LTD. |
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CP01 | Change in the name or title of a patent holder |
Address after: 570216 No. 8 workshop, Haikou Free Trade Zone, Hainan Patentee after: Hainan Ling Kang Pharmaceutical Group Limited by Share Ltd. Address before: 570216 No. 8 workshop, Haikou Free Trade Zone, Hainan Patentee before: Hainan Lingkang Pharmaceutical Co.,Ltd. |
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TR01 | Transfer of patent right |
Effective date of registration: 20130926 Address after: 570216 Hainan Province, Haikou city Jinpan Industrial Development Zone Industrial Village No. 3-6 building Patentee after: Hainan Lingkang Pharmaceutical Co.,Ltd. Address before: 570216 No. 8 workshop, Haikou Free Trade Zone, Hainan Patentee before: Hainan Ling Kang Pharmaceutical Group Limited by Share Ltd. |
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CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120926 Termination date: 20160715 |
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CF01 | Termination of patent right due to non-payment of annual fee |