JP2002510692A5 - - Google Patents
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- Publication number
- JP2002510692A5 JP2002510692A5 JP2000542325A JP2000542325A JP2002510692A5 JP 2002510692 A5 JP2002510692 A5 JP 2002510692A5 JP 2000542325 A JP2000542325 A JP 2000542325A JP 2000542325 A JP2000542325 A JP 2000542325A JP 2002510692 A5 JP2002510692 A5 JP 2002510692A5
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- alkyl
- aryl
- reaction
- 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
- 150000001875 compounds Chemical class 0.000 description 29
- 238000000034 method Methods 0.000 description 21
- 125000000217 alkyl group Chemical group 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- -1 aryl amide Chemical class 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 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 description 9
- 229910052739 hydrogen Inorganic materials 0.000 description 9
- JNTOCHDNEULJHD-UHFFFAOYSA-N Penciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(CCC(CO)CO)C=N2 JNTOCHDNEULJHD-UHFFFAOYSA-N 0.000 description 7
- 229960004396 famciclovir Drugs 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- 230000008707 rearrangement Effects 0.000 description 7
- RYYIULNRIVUMTQ-UHFFFAOYSA-N 6-chloroguanine Chemical compound NC1=NC(Cl)=C2N=CNC2=N1 RYYIULNRIVUMTQ-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- 150000003212 purines Chemical class 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 150000001335 aliphatic alkanes Chemical class 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 229960001179 penciclovir Drugs 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000006462 rearrangement reaction Methods 0.000 description 4
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 125000005104 aryl silyl group Chemical group 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 125000005116 aryl carbamoyl group Chemical group 0.000 description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 2
- 125000005110 aryl thio group Chemical group 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 0 *C(*)=CC[n]1c2nc(*)nc(*)c2nc1 Chemical compound *C(*)=CC[n]1c2nc(*)nc(*)c2nc1 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- ODENUAVVDSGQFD-UHFFFAOYSA-N 6-chloro-9-[2-(2,2-dimethyl-1,3-dioxan-5-ylidene)ethyl]purin-2-amine Chemical compound C1OC(C)(C)OCC1=CCN1C2=NC(N)=NC(Cl)=C2N=C1 ODENUAVVDSGQFD-UHFFFAOYSA-N 0.000 description 1
- VPTQFSPUAWLBAU-UHFFFAOYSA-N C(C)=C1OC(OCC1)(C)C Chemical compound C(C)=C1OC(OCC1)(C)C VPTQFSPUAWLBAU-UHFFFAOYSA-N 0.000 description 1
- BPYJOGXSJBCPEX-UHFFFAOYSA-N CCC(CC)COC(=O)C(CCN1C=NC2=C1N=C(N=C2Cl)N)(C(=O)O)C(=O)O Chemical compound CCC(CC)COC(=O)C(CCN1C=NC2=C1N=C(N=C2Cl)N)(C(=O)O)C(=O)O BPYJOGXSJBCPEX-UHFFFAOYSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SUAKHGWARZSWIH-UHFFFAOYSA-N N,N‐diethylformamide Chemical compound CCN(CC)C=O SUAKHGWARZSWIH-UHFFFAOYSA-N 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- DTCCTWLFXXLEKC-UHFFFAOYSA-N NC=C(CO)CO Chemical compound NC=C(CO)CO DTCCTWLFXXLEKC-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 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 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 125000005103 alkyl silyl group Chemical group 0.000 description 1
- 125000005233 alkylalcohol group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- SALNWJHEVGXTER-UHFFFAOYSA-N dimethyl 2-[2-(2-amino-6-chloropurin-9-yl)ethyl]propanedioate Chemical compound N1=C(N)N=C2N(CCC(C(=O)OC)C(=O)OC)C=NC2=C1Cl SALNWJHEVGXTER-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- WUOIAOOSKMHJOV-UHFFFAOYSA-N ethyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(CC)C1=CC=CC=C1 WUOIAOOSKMHJOV-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 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
- 239000002699 waste material Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9807116.0 | 1998-04-02 | ||
| GBGB9807116.0A GB9807116D0 (en) | 1998-04-02 | 1998-04-02 | Novel process |
| PCT/EP1999/002309 WO1999051604A2 (en) | 1998-04-02 | 1999-03-30 | Process for the production of purine derivatives |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2002510692A JP2002510692A (ja) | 2002-04-09 |
| JP2002510692A5 true JP2002510692A5 (https=) | 2006-05-18 |
| JP4459439B2 JP4459439B2 (ja) | 2010-04-28 |
Family
ID=10829765
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000542325A Expired - Fee Related JP4459439B2 (ja) | 1998-04-02 | 1999-03-30 | プリン誘導体の製造方法 |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US6437125B1 (https=) |
| EP (1) | EP1068210B1 (https=) |
| JP (1) | JP4459439B2 (https=) |
| KR (1) | KR100613812B1 (https=) |
| CN (1) | CN1125068C (https=) |
| AT (1) | ATE268332T1 (https=) |
| AU (1) | AU3605199A (https=) |
| BR (1) | BR9908959A (https=) |
| CA (1) | CA2323965A1 (https=) |
| DE (1) | DE69917765T2 (https=) |
| DK (1) | DK1068210T3 (https=) |
| ES (1) | ES2222702T3 (https=) |
| GB (1) | GB9807116D0 (https=) |
| IL (1) | IL138289A0 (https=) |
| PT (1) | PT1068210E (https=) |
| WO (1) | WO1999051604A2 (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1288215B8 (en) | 2001-08-30 | 2005-04-06 | Ajinomoto Co., Inc. | Production method of famciclovir and production and crystallization method of intermediate therefor |
| EP1532151A2 (en) * | 2002-08-26 | 2005-05-25 | Teva Pharmaceutical Industries Limited | Crystalline solid famciclovir forms i, ii, iii and preparation thereof |
| KR20080091298A (ko) * | 2004-05-18 | 2008-10-09 | 테바 파마슈티컬 인더스트리즈 리미티드 | 결정성 고체 팜시클로버의 제조를 위한 건조방법 |
| GB2426247A (en) * | 2005-05-20 | 2006-11-22 | Arrow Int Ltd | Methods of preparing purine derivatives such as famciclovir |
| CN110386935A (zh) * | 2018-04-20 | 2019-10-29 | 重庆常捷医药有限公司 | 一种泛昔洛韦中间体的合成方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5684153A (en) | 1984-08-16 | 1997-11-04 | Beecham Group Plc | Process for the preparation of purine derivatives |
| 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 |
| GB8817607D0 (en) * | 1988-07-23 | 1988-09-01 | Beecham Group Plc | Novel process |
| US5688948A (en) * | 1991-09-18 | 1997-11-18 | Ajinomoto Co., Inc. | Process for isomerizing acyclic nucleosides and process for separating purine nucleosides |
| GB9407698D0 (en) | 1994-04-19 | 1994-06-15 | Smithkline Beecham Plc | Pharmaceuticals |
| EP0827960A1 (en) * | 1996-09-10 | 1998-03-11 | Ajinomoto Co., Inc. | Process for producing purine derivatives |
-
1998
- 1998-04-02 GB GBGB9807116.0A patent/GB9807116D0/en not_active Ceased
-
1999
- 1999-03-30 KR KR1020007010706A patent/KR100613812B1/ko not_active Expired - Fee Related
- 1999-03-30 AT AT99917959T patent/ATE268332T1/de not_active IP Right Cessation
- 1999-03-30 ES ES99917959T patent/ES2222702T3/es not_active Expired - Lifetime
- 1999-03-30 IL IL13828999A patent/IL138289A0/xx not_active IP Right Cessation
- 1999-03-30 PT PT99917959T patent/PT1068210E/pt unknown
- 1999-03-30 AU AU36051/99A patent/AU3605199A/en not_active Abandoned
- 1999-03-30 CN CN99804402A patent/CN1125068C/zh not_active Expired - Fee Related
- 1999-03-30 EP EP19990917959 patent/EP1068210B1/en not_active Expired - Lifetime
- 1999-03-30 CA CA002323965A patent/CA2323965A1/en not_active Abandoned
- 1999-03-30 DK DK99917959T patent/DK1068210T3/da active
- 1999-03-30 BR BR9908959-9A patent/BR9908959A/pt not_active Application Discontinuation
- 1999-03-30 JP JP2000542325A patent/JP4459439B2/ja not_active Expired - Fee Related
- 1999-03-30 WO PCT/EP1999/002309 patent/WO1999051604A2/en not_active Ceased
- 1999-03-30 DE DE69917765T patent/DE69917765T2/de not_active Expired - Fee Related
- 1999-03-30 US US09/623,700 patent/US6437125B1/en not_active Expired - Lifetime
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