NO315000B1 - Fremgangsmåte for fremstilling av puriner samt mellomprodukter for fremstillingen - Google Patents
Fremgangsmåte for fremstilling av puriner samt mellomprodukter for fremstillingen Download PDFInfo
- Publication number
- NO315000B1 NO315000B1 NO19964395A NO964395A NO315000B1 NO 315000 B1 NO315000 B1 NO 315000B1 NO 19964395 A NO19964395 A NO 19964395A NO 964395 A NO964395 A NO 964395A NO 315000 B1 NO315000 B1 NO 315000B1
- Authority
- NO
- Norway
- Prior art keywords
- formula
- compound
- amino
- preparation
- alkyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 20
- 238000002360 preparation method Methods 0.000 title claims description 13
- 239000000543 intermediate Substances 0.000 title 1
- 150000003212 purines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 12
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 7
- GGXKWVWZWMLJEH-UHFFFAOYSA-N famcyclovir Chemical compound N1=C(N)N=C2N(CCC(COC(=O)C)COC(C)=O)C=NC2=C1 GGXKWVWZWMLJEH-UHFFFAOYSA-N 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- JNTOCHDNEULJHD-UHFFFAOYSA-N Penciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(CCC(CO)CO)C=N2 JNTOCHDNEULJHD-UHFFFAOYSA-N 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 238000006114 decarboxylation reaction Methods 0.000 claims description 4
- 229960004396 famciclovir Drugs 0.000 claims description 4
- 125000002467 phosphate group Chemical class [H]OP(=O)(O[H])O[*] 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 150000002431 hydrogen Chemical group 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- 229960001179 penciclovir Drugs 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 7
- RYYIULNRIVUMTQ-UHFFFAOYSA-N 6-chloroguanine Chemical compound NC1=NC(Cl)=C2N=CNC2=N1 RYYIULNRIVUMTQ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- KXPSHSVVYGZKAV-UHFFFAOYSA-N [2-(acetyloxymethyl)-4-(2-amino-6-chloropurin-9-yl)butyl] acetate Chemical compound N1=C(N)N=C2N(CCC(COC(=O)C)COC(C)=O)C=NC2=C1Cl KXPSHSVVYGZKAV-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- MWBWWFOAEOYUST-UHFFFAOYSA-N 2-aminopurine Chemical compound NC1=NC=C2N=CNC2=N1 MWBWWFOAEOYUST-UHFFFAOYSA-N 0.000 description 1
- YGKBJPKABWZOSK-UHFFFAOYSA-N 9-(4-hydroxy-3-hydroxymethylbut-l-yl) guanine penciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(CCC(CO)CO)C=N2.N1C(N)=NC(=O)C2=C1N(CCC(CO)CO)C=N2 YGKBJPKABWZOSK-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004440 column chromatography Methods 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
- 239000012043 crude product Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229940127073 nucleoside analogue Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- VIMWZZMUASPQPL-UHFFFAOYSA-N triethyl 3-bromopropane-1,1,1-tricarboxylate Chemical compound CCOC(=O)C(CCBr)(C(=O)OCC)C(=O)OCC VIMWZZMUASPQPL-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Chemical Treatment Of Metals (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9407698A GB9407698D0 (en) | 1994-04-19 | 1994-04-19 | Pharmaceuticals |
PCT/EP1995/001840 WO1995028402A2 (en) | 1994-04-19 | 1995-04-19 | Preparation of purines |
Publications (3)
Publication Number | Publication Date |
---|---|
NO964395L NO964395L (no) | 1996-10-15 |
NO964395D0 NO964395D0 (no) | 1996-10-15 |
NO315000B1 true NO315000B1 (no) | 2003-06-23 |
Family
ID=10753741
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19964395A NO315000B1 (no) | 1994-04-19 | 1996-10-15 | Fremgangsmåte for fremstilling av puriner samt mellomprodukter for fremstillingen |
Country Status (40)
Country | Link |
---|---|
US (2) | US6846927B1 (xx) |
EP (1) | EP0756597B1 (xx) |
JP (1) | JP3936734B2 (xx) |
KR (1) | KR100327147B1 (xx) |
CN (1) | CN1045963C (xx) |
AP (2) | AP582A (xx) |
AT (1) | ATE201209T1 (xx) |
AU (1) | AU691000B2 (xx) |
BG (1) | BG63464B1 (xx) |
BR (1) | BR9507494A (xx) |
CA (1) | CA2188181C (xx) |
CZ (1) | CZ287674B6 (xx) |
DE (1) | DE69520945T2 (xx) |
DK (1) | DK0756597T3 (xx) |
DZ (1) | DZ1872A1 (xx) |
EG (1) | EG20938A (xx) |
ES (1) | ES2158948T3 (xx) |
FI (1) | FI119691B (xx) |
GB (1) | GB9407698D0 (xx) |
GR (1) | GR3036338T3 (xx) |
HK (1) | HK1012348A1 (xx) |
HU (1) | HU226209B1 (xx) |
IL (1) | IL113409A (xx) |
IN (1) | IN183830B (xx) |
MA (1) | MA23518A1 (xx) |
MX (1) | MX9604942A (xx) |
MY (1) | MY128846A (xx) |
NO (1) | NO315000B1 (xx) |
NZ (1) | NZ287858A (xx) |
OA (1) | OA10376A (xx) |
PL (1) | PL181219B1 (xx) |
PT (1) | PT756597E (xx) |
RO (1) | RO118950B1 (xx) |
RU (1) | RU2158266C2 (xx) |
SA (1) | SA95150619B1 (xx) |
SK (1) | SK283193B6 (xx) |
TW (1) | TW311138B (xx) |
UA (1) | UA47401C2 (xx) |
WO (1) | WO1995028402A2 (xx) |
ZA (1) | ZA953110B (xx) |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9615253D0 (en) * | 1996-07-20 | 1996-09-04 | Smithkline Beecham Plc | Pharmaceuticals |
GB9615276D0 (en) * | 1996-07-20 | 1996-09-04 | Smithkline Beecham Plc | Pharmaceuticals |
GB9807116D0 (en) | 1998-04-02 | 1998-06-03 | Smithkline Beecham Plc | Novel process |
GB9807114D0 (en) | 1998-04-02 | 1998-06-03 | Smithkline Beecham Plc | Novel process |
AU2003268213A1 (en) * | 2002-08-26 | 2004-03-11 | Teva Pharmaceutical Industries Ltd. | Crystalline solid famciclovir forms i, ii, iii and preparation thereof |
US20040266795A1 (en) * | 2003-04-30 | 2004-12-30 | Genny Shamai | Process for the preparation of famciclovir |
US20050143400A1 (en) * | 2003-09-04 | 2005-06-30 | Genny Shamai | Process for preparing famciclovir |
US7458839B2 (en) * | 2006-02-21 | 2008-12-02 | Fci Americas Technology, Inc. | Electrical connectors having power contacts with alignment and/or restraining features |
US20050215787A1 (en) * | 2004-03-26 | 2005-09-29 | Joshi Ramesh A | An improved process for the preparation of purines |
JP2007538087A (ja) * | 2004-05-18 | 2007-12-27 | テバ ファーマシューティカル インダストリーズ リミティド | 結晶固形ファムシクロビルを調製するための乾燥方法 |
GB2426247A (en) * | 2005-05-20 | 2006-11-22 | Arrow Int Ltd | Methods of preparing purine derivatives such as famciclovir |
CN102070636B (zh) * | 2011-01-17 | 2012-05-23 | 浙江大学 | 喷昔洛韦的制备方法 |
CN104086552B (zh) * | 2014-07-31 | 2016-01-13 | 济南兆康医药科技有限公司 | 一种喷昔洛韦的精制方法 |
CN104496991A (zh) * | 2014-11-04 | 2015-04-08 | 常州康丽制药有限公司 | 高品质2-氨基-6-氯-9-(4-羟基-3–羟甲基丁基)嘌呤的制备方法 |
CN104744472A (zh) * | 2015-03-12 | 2015-07-01 | 常州康丽制药有限公司 | 高品质2-氨基-6-氯-9-(4-羟基-3-羟甲基丁基)嘌呤的制备方法 |
CN108314685B (zh) * | 2018-03-16 | 2020-08-25 | 上药康丽(常州)药业有限公司 | 一种2-氨基-6-氯-9-(4-乙酰氧基-3-乙酰氧甲基丁基)嘌呤的制备方法 |
CN110713490A (zh) * | 2018-07-12 | 2020-01-21 | 浙江医药股份有限公司新昌制药厂 | 一种喷昔洛韦的制备方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0141927B1 (en) * | 1983-08-18 | 1991-10-30 | Beecham Group Plc | Antiviral guanine derivatives |
EP0182024B1 (en) * | 1984-09-20 | 1991-04-03 | Beecham Group Plc | Purine derivatives and their pharmaceutical use |
ES2098219T3 (es) * | 1987-08-01 | 1997-05-01 | Beecham Group Plc | Compuestos de purina y su preparacion. |
GB8817607D0 (en) * | 1988-07-23 | 1988-09-01 | Beecham Group Plc | Novel process |
GB8822236D0 (en) * | 1988-09-21 | 1988-10-26 | Beecham Group Plc | Chemical process |
-
1994
- 1994-04-19 GB GB9407698A patent/GB9407698D0/en active Pending
-
1995
- 1995-04-12 DZ DZ950040A patent/DZ1872A1/fr active
- 1995-04-13 AP APAP/P/1995/000730A patent/AP582A/en active
- 1995-04-17 MY MYPI95000990A patent/MY128846A/en unknown
- 1995-04-17 TW TW084103750A patent/TW311138B/zh not_active IP Right Cessation
- 1995-04-17 MA MA23846A patent/MA23518A1/fr unknown
- 1995-04-18 ZA ZA953110A patent/ZA953110B/xx unknown
- 1995-04-18 IN IN705DE1995 patent/IN183830B/en unknown
- 1995-04-18 IL IL11340995A patent/IL113409A/xx not_active IP Right Cessation
- 1995-04-19 MX MX9604942A patent/MX9604942A/es active IP Right Grant
- 1995-04-19 CZ CZ19963053A patent/CZ287674B6/cs not_active IP Right Cessation
- 1995-04-19 KR KR1019960705948A patent/KR100327147B1/ko not_active IP Right Cessation
- 1995-04-19 UA UA96103899A patent/UA47401C2/uk unknown
- 1995-04-19 WO PCT/EP1995/001840 patent/WO1995028402A2/en active IP Right Grant
- 1995-04-19 RU RU96121936/04A patent/RU2158266C2/ru active
- 1995-04-19 EP EP95921751A patent/EP0756597B1/en not_active Expired - Lifetime
- 1995-04-19 RO RO96-02001A patent/RO118950B1/ro unknown
- 1995-04-19 AT AT95921751T patent/ATE201209T1/de active
- 1995-04-19 AU AU26706/95A patent/AU691000B2/en not_active Expired
- 1995-04-19 AP APAP/P/1996/000870A patent/AP703A/en active
- 1995-04-19 ES ES95921751T patent/ES2158948T3/es not_active Expired - Lifetime
- 1995-04-19 EG EG32695A patent/EG20938A/xx active
- 1995-04-19 PT PT95921751T patent/PT756597E/pt unknown
- 1995-04-19 HU HU9602891A patent/HU226209B1/hu unknown
- 1995-04-19 SK SK1332-96A patent/SK283193B6/sk not_active IP Right Cessation
- 1995-04-19 CA CA002188181A patent/CA2188181C/en not_active Expired - Lifetime
- 1995-04-19 NZ NZ287858A patent/NZ287858A/en not_active IP Right Cessation
- 1995-04-19 DK DK95921751T patent/DK0756597T3/da active
- 1995-04-19 CN CN95193489A patent/CN1045963C/zh not_active Expired - Lifetime
- 1995-04-19 PL PL95316943A patent/PL181219B1/pl unknown
- 1995-04-19 DE DE69520945T patent/DE69520945T2/de not_active Expired - Lifetime
- 1995-04-19 JP JP52673895A patent/JP3936734B2/ja not_active Expired - Lifetime
- 1995-04-19 BR BR9507494A patent/BR9507494A/pt unknown
- 1995-04-26 SA SA95150619A patent/SA95150619B1/ar unknown
-
1996
- 1996-10-15 NO NO19964395A patent/NO315000B1/no not_active IP Right Cessation
- 1996-10-18 BG BG100926A patent/BG63464B1/bg unknown
- 1996-10-18 FI FI964193A patent/FI119691B/fi not_active IP Right Cessation
- 1996-10-18 OA OA60905A patent/OA10376A/en unknown
-
1998
- 1998-12-15 HK HK98113459A patent/HK1012348A1/xx not_active IP Right Cessation
-
1999
- 1999-03-11 US US09/265,926 patent/US6846927B1/en not_active Expired - Fee Related
-
2001
- 2001-08-07 GR GR20010401190T patent/GR3036338T3/el unknown
-
2004
- 2004-12-14 US US11/011,352 patent/US7355043B2/en not_active Expired - Fee Related
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
MK1K | Patent expired |