CN105693723A - 一种cbz-缬更昔洛韦的制备方法 - Google Patents
一种cbz-缬更昔洛韦的制备方法 Download PDFInfo
- Publication number
- CN105693723A CN105693723A CN201610246500.2A CN201610246500A CN105693723A CN 105693723 A CN105693723 A CN 105693723A CN 201610246500 A CN201610246500 A CN 201610246500A CN 105693723 A CN105693723 A CN 105693723A
- Authority
- CN
- China
- Prior art keywords
- valganciclovir
- cbz
- preparation
- white solid
- monoesters
- 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
- 229960002149 valganciclovir Drugs 0.000 title claims abstract description 48
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 37
- 239000007787 solid Substances 0.000 claims abstract description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 20
- WPVFJKSGQUFQAP-GKAPJAKFSA-N Valcyte Chemical compound N1C(N)=NC(=O)C2=C1N(COC(CO)COC(=O)[C@@H](N)C(C)C)C=N2 WPVFJKSGQUFQAP-GKAPJAKFSA-N 0.000 claims abstract description 15
- 238000003756 stirring Methods 0.000 claims abstract description 15
- 239000012065 filter cake Substances 0.000 claims abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims abstract description 12
- 239000000706 filtrate Substances 0.000 claims abstract description 11
- 238000010992 reflux Methods 0.000 claims abstract description 7
- 239000000376 reactant Substances 0.000 claims abstract description 5
- 229960002963 ganciclovir Drugs 0.000 claims description 22
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 claims description 22
- 239000002244 precipitate Substances 0.000 claims description 20
- 238000001914 filtration Methods 0.000 claims description 18
- 239000010410 layer Substances 0.000 claims description 16
- 239000012044 organic layer Substances 0.000 claims description 16
- 239000000047 product Substances 0.000 claims description 13
- 230000001105 regulatory effect Effects 0.000 claims description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 239000000284 extract Substances 0.000 claims description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 230000000630 rising effect Effects 0.000 claims description 6
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- CANZBRDGRHNSGZ-NSHDSACASA-N (2s)-3-methyl-2-(phenylmethoxycarbonylamino)butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 CANZBRDGRHNSGZ-NSHDSACASA-N 0.000 claims description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 13
- 238000003786 synthesis reaction Methods 0.000 abstract description 13
- 239000002699 waste material Substances 0.000 abstract description 8
- 239000003344 environmental pollutant Substances 0.000 abstract description 4
- 231100000719 pollutant Toxicity 0.000 abstract description 4
- 238000000967 suction filtration Methods 0.000 abstract 2
- 239000003513 alkali Substances 0.000 abstract 1
- 238000006482 condensation reaction Methods 0.000 abstract 1
- 238000001816 cooling Methods 0.000 abstract 1
- 150000005690 diesters Chemical class 0.000 abstract 1
- 238000000605 extraction Methods 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 239000002253 acid Substances 0.000 description 24
- 150000002148 esters Chemical class 0.000 description 23
- 238000000034 method Methods 0.000 description 14
- 229960004295 valine Drugs 0.000 description 8
- 241000701022 Cytomegalovirus Species 0.000 description 7
- 208000030507 AIDS Diseases 0.000 description 5
- ZORWARFPXPVJLW-MTFPJWTKSA-N [2-[(2-amino-6-oxo-3h-purin-9-yl)methoxy]-3-hydroxypropyl] (2s)-2-amino-3-methylbutanoate;hydron;chloride Chemical compound Cl.N1C(N)=NC(=O)C2=C1N(COC(CO)COC(=O)[C@@H](N)C(C)C)C=N2 ZORWARFPXPVJLW-MTFPJWTKSA-N 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 229960004983 valganciclovir hydrochloride Drugs 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- -1 valyl ester Chemical class 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000036737 immune function Effects 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- 238000011017 operating method Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 206010048843 Cytomegalovirus chorioretinitis Diseases 0.000 description 1
- 206010011831 Cytomegalovirus infection Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000001860 Eye Infections Diseases 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 206010038910 Retinitis Diseases 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 208000001763 cytomegalovirus retinitis Diseases 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000011090 industrial biotechnology method and process Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 229950003188 isovaleryl diethylamide Drugs 0.000 description 1
- GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (6)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610246500.2A CN105693723B (zh) | 2016-04-20 | 2016-04-20 | 一种cbz-缬更昔洛韦单酯的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610246500.2A CN105693723B (zh) | 2016-04-20 | 2016-04-20 | 一种cbz-缬更昔洛韦单酯的制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105693723A true CN105693723A (zh) | 2016-06-22 |
CN105693723B CN105693723B (zh) | 2019-02-26 |
Family
ID=56217190
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CN201610246500.2A Active CN105693723B (zh) | 2016-04-20 | 2016-04-20 | 一种cbz-缬更昔洛韦单酯的制备方法 |
Country Status (1)
Country | Link |
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CN (1) | CN105693723B (zh) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102070635A (zh) * | 2009-11-19 | 2011-05-25 | 浙江车头制药有限公司 | 一种更昔洛韦缬氨酸酯衍生物的制备方法 |
US20110207931A1 (en) * | 2010-02-23 | 2011-08-25 | Srinivas Katkam | Preparation of valganciclovir and its salts |
CN105085524A (zh) * | 2014-05-13 | 2015-11-25 | 重庆圣华曦药业股份有限公司 | 一种制备高纯度盐酸缬更昔洛韦的方法 |
-
2016
- 2016-04-20 CN CN201610246500.2A patent/CN105693723B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102070635A (zh) * | 2009-11-19 | 2011-05-25 | 浙江车头制药有限公司 | 一种更昔洛韦缬氨酸酯衍生物的制备方法 |
US20110207931A1 (en) * | 2010-02-23 | 2011-08-25 | Srinivas Katkam | Preparation of valganciclovir and its salts |
CN105085524A (zh) * | 2014-05-13 | 2015-11-25 | 重庆圣华曦药业股份有限公司 | 一种制备高纯度盐酸缬更昔洛韦的方法 |
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Publication number | Publication date |
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CN105693723B (zh) | 2019-02-26 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A Preparation Method of CBZ Valganciclovir Monoester Granted publication date: 20190226 Pledgee: China Postal Savings Bank Limited by Share Ltd. Anqing branch Pledgor: ANHUI HAIKANG PHARMACEUTICAL Co.,Ltd. Registration number: Y2024980000631 |
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PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
CP03 | Change of name, title or address |
Address after: 246000 No.21, Huancheng West Road, Daguan District, Anqing City, Anhui Province Patentee after: Anhui Haikang Pharmaceutical Co.,Ltd. Country or region after: China Address before: 246000 No.21, Huancheng West Road, Daguan District, Anqing City, Anhui Province Patentee before: ANHUI HAIKANG PHARMACEUTICAL Co.,Ltd. Country or region before: China |
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CP03 | Change of name, title or address |