CN105693724B - 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
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- CN105693724B CN105693724B CN201610246652.2A CN201610246652A CN105693724B CN 105693724 B CN105693724 B CN 105693724B CN 201610246652 A CN201610246652 A CN 201610246652A CN 105693724 B CN105693724 B CN 105693724B
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- China
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- water
- cbz
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- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 46
- 238000006243 chemical reaction Methods 0.000 claims abstract description 41
- 239000000047 product Substances 0.000 claims abstract description 17
- 238000003756 stirring Methods 0.000 claims abstract description 15
- 238000000967 suction filtration Methods 0.000 claims abstract description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000009835 boiling Methods 0.000 claims abstract description 12
- 239000007787 solid Substances 0.000 claims abstract description 12
- 239000012065 filter cake Substances 0.000 claims abstract description 11
- HDPNBNXLBDFELL-UHFFFAOYSA-N 1,1,1-trimethoxyethane Chemical compound COC(C)(OC)OC HDPNBNXLBDFELL-UHFFFAOYSA-N 0.000 claims abstract description 9
- 235000014393 valine Nutrition 0.000 claims abstract description 7
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims abstract description 6
- 238000001816 cooling Methods 0.000 claims abstract description 6
- 239000000706 filtrate Substances 0.000 claims abstract description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims abstract description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- 239000000243 solution Substances 0.000 claims description 13
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 4
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 238000004064 recycling Methods 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims 1
- 238000010025 steaming Methods 0.000 claims 1
- 229960002149 valganciclovir Drugs 0.000 abstract description 20
- 230000015572 biosynthetic process Effects 0.000 abstract description 13
- 238000003786 synthesis reaction Methods 0.000 abstract description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 10
- 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 abstract description 9
- 230000007062 hydrolysis Effects 0.000 abstract description 7
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 7
- 239000012153 distilled water Substances 0.000 abstract description 4
- 239000003344 environmental pollutant Substances 0.000 abstract description 4
- 231100000719 pollutant Toxicity 0.000 abstract description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 abstract 1
- 238000001556 precipitation Methods 0.000 abstract 1
- 150000003680 valines Chemical class 0.000 abstract 1
- 239000002253 acid Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 9
- 241000701022 Cytomegalovirus Species 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 208000030507 AIDS Diseases 0.000 description 4
- 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 4
- 238000004821 distillation Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 229960004983 valganciclovir hydrochloride Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- -1 valyl ester Chemical class 0.000 description 3
- 241000700605 Viruses Species 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000036737 immune function Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000002699 waste material Substances 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
- 206010061218 Inflammation Diseases 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 208000001763 cytomegalovirus retinitis Diseases 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229940079593 drug Drugs 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
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229950003188 isovaleryl diethylamide Drugs 0.000 description 1
- 210000004185 liver Anatomy 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
- 238000011017 operating method Methods 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN201610246652.2A CN105693724B (zh) | 2016-04-20 | 2016-04-20 | 一种cbz‑缬更昔洛韦的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610246652.2A CN105693724B (zh) | 2016-04-20 | 2016-04-20 | 一种cbz‑缬更昔洛韦的制备方法 |
Publications (2)
Publication Number | Publication Date |
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CN105693724A CN105693724A (zh) | 2016-06-22 |
CN105693724B true CN105693724B (zh) | 2017-08-11 |
Family
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CN201610246652.2A Active CN105693724B (zh) | 2016-04-20 | 2016-04-20 | 一种cbz‑缬更昔洛韦的制备方法 |
Country Status (1)
Country | Link |
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CN (1) | CN105693724B (zh) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5840890A (en) * | 1996-01-26 | 1998-11-24 | Syntex (U.S.A.) Inc. | Process for preparing a 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol derivative |
CN103562207A (zh) * | 2011-05-31 | 2014-02-05 | 法尔玛赞公司 | 用于制备缬更昔洛韦的2-氨基-9-((2-苯基-1,3-二噁烷-5-基氧基)甲基)-1h-嘌呤-6(9h)-酮化合物的制备方法 |
-
2016
- 2016-04-20 CN CN201610246652.2A patent/CN105693724B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5840890A (en) * | 1996-01-26 | 1998-11-24 | Syntex (U.S.A.) Inc. | Process for preparing a 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol derivative |
CN103562207A (zh) * | 2011-05-31 | 2014-02-05 | 法尔玛赞公司 | 用于制备缬更昔洛韦的2-氨基-9-((2-苯基-1,3-二噁烷-5-基氧基)甲基)-1h-嘌呤-6(9h)-酮化合物的制备方法 |
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CN105693724A (zh) | 2016-06-22 |
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Legal Events
Date | Code | Title | Description |
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C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
TR01 | Transfer of patent right |
Effective date of registration: 20190410 Address after: 246002 No. 8, 9 and 10 Building 14, Daguanting Phase II, Daguanting District, Anqing City, Anhui Province Patentee after: ANQING XUANYU PHARMACEUTICAL TECHNOLOGY Co.,Ltd. Address before: 246000 No. 21 Huancheng West Road, Daguan District, Anqing City, Anhui Province Patentee before: ANHUI HAIKANG PHARMACEUTICAL Co.,Ltd. |
|
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20190710 Address after: 246000 No. 21 Huancheng West Road, Daguan District, Anqing City, Anhui Province Patentee after: ANHUI HAIKANG PHARMACEUTICAL Co.,Ltd. Address before: 246002 No. 8, 9 and 10 Building 14, Daguanting Phase II, Daguanting District, Anqing City, Anhui Province Patentee before: ANQING XUANYU PHARMACEUTICAL TECHNOLOGY Co.,Ltd. |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Preparation method of CBZ-valganciclovir Effective date of registration: 20190906 Granted publication date: 20170811 Pledgee: Xingye Bank Limited by Share Ltd. Anqing branch Pledgor: ANHUI HAIKANG PHARMACEUTICAL Co.,Ltd. Registration number: Y2019340000051 |
|
CP03 | Change of name, title or address | ||
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 |