GB1570219A - Method of producing 5-fluorouracil derivatives - Google Patents
Method of producing 5-fluorouracil derivatives Download PDFInfo
- Publication number
- GB1570219A GB1570219A GB47197/76A GB4719776A GB1570219A GB 1570219 A GB1570219 A GB 1570219A GB 47197/76 A GB47197/76 A GB 47197/76A GB 4719776 A GB4719776 A GB 4719776A GB 1570219 A GB1570219 A GB 1570219A
- Authority
- GB
- United Kingdom
- Prior art keywords
- fluorouracil
- furyl
- tetrahydro
- bis
- solvolysis
- 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.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims description 121
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical class FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 title claims description 48
- 229960002949 fluorouracil Drugs 0.000 claims description 49
- 239000002904 solvent Substances 0.000 claims description 37
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 claims description 35
- 238000006243 chemical reaction Methods 0.000 claims description 33
- 238000003797 solvolysis reaction Methods 0.000 claims description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 24
- WFWLQNSHRPWKFK-UHFFFAOYSA-N Tegafur Chemical compound O=C1NC(=O)C(F)=CN1C1OCCC1 WFWLQNSHRPWKFK-UHFFFAOYSA-N 0.000 claims description 24
- FLMBDTNCANYTCP-UHFFFAOYSA-N 5-fluoro-1,3-bis(oxolan-2-yl)pyrimidine-2,4-dione Chemical compound O=C1N(C2OCCC2)C(=O)C(F)=CN1C1CCCO1 FLMBDTNCANYTCP-UHFFFAOYSA-N 0.000 claims description 21
- 238000010438 heat treatment Methods 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
- 230000002378 acidificating effect Effects 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000000047 product Substances 0.000 claims description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000000741 silica gel Substances 0.000 claims description 6
- 229910002027 silica gel Inorganic materials 0.000 claims description 6
- 239000007795 chemical reaction product Substances 0.000 claims description 4
- 238000004809 thin layer chromatography Methods 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- 150000001408 amides Chemical group 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 5
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims 4
- 239000000376 reactant Substances 0.000 claims 4
- 238000000926 separation method Methods 0.000 claims 4
- 229940035893 uracil Drugs 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 239000003960 organic solvent Substances 0.000 claims 1
- 239000002798 polar solvent Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 239000004575 stone Substances 0.000 claims 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- ZVAKZVDJIUFFFP-UHFFFAOYSA-N 2-chlorooxolane Chemical compound ClC1CCCO1 ZVAKZVDJIUFFFP-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001103 continuous-wave nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14271775A JPS5268188A (en) | 1975-11-28 | 1975-11-28 | Preparation of 1-(tetrahydro-2-furyl)-5-fluorouracil |
| JP526076A JPS5289679A (en) | 1976-01-19 | 1976-01-19 | Preparation of 5-fluorouracil derivatives |
| JP8386376A JPS539778A (en) | 1976-07-13 | 1976-07-13 | Preparation of 5-fluorouracil derivativds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1570219A true GB1570219A (en) | 1980-06-25 |
Family
ID=27276677
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB47197/76A Expired GB1570219A (en) | 1975-11-28 | 1976-11-12 | Method of producing 5-fluorouracil derivatives |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US4249006A (en, 2012) |
| AT (1) | AT346858B (en, 2012) |
| AU (1) | AU501833B2 (en, 2012) |
| BE (1) | BE848662A (en, 2012) |
| CA (1) | CA1122983A (en, 2012) |
| CH (1) | CH616936A5 (en, 2012) |
| DE (1) | DE2653398C2 (en, 2012) |
| DK (1) | DK140635B (en, 2012) |
| FR (1) | FR2332991A1 (en, 2012) |
| GB (1) | GB1570219A (en, 2012) |
| GR (1) | GR62855B (en, 2012) |
| HK (1) | HK11283A (en, 2012) |
| HU (1) | HU176890B (en, 2012) |
| IE (1) | IE45046B1 (en, 2012) |
| MX (1) | MX3873E (en, 2012) |
| MY (1) | MY8400088A (en, 2012) |
| NL (1) | NL7613285A (en, 2012) |
| NO (1) | NO144887C (en, 2012) |
| PH (1) | PH12998A (en, 2012) |
| PL (1) | PL104613B1 (en, 2012) |
| PT (1) | PT65883B (en, 2012) |
| SE (1) | SE423389B (en, 2012) |
| SG (1) | SG783G (en, 2012) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004103382A1 (en) * | 2003-05-20 | 2004-12-02 | Aronex Pharmaceuticals, Inc. | Combination chemotherapy comprising 5-fluorouracil or a derivative thereof and a liposomal platinum complex |
| CN103159746B (zh) * | 2011-12-12 | 2015-09-02 | 山东新时代药业有限公司 | 一种工业法合成替加氟的方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1695297C3 (de) * | 1968-01-10 | 1978-12-07 | Institut Organitscheskogo Sinteza, Riga (Sowjetunion) | 5-Fluor-l-(2-tetrahydrofuryl)-uracil und dessen Alkal'imetaUsalze, Verfahren zu deren Herstellung und diese enthaltende Mittel |
| US3912734A (en) * | 1972-11-20 | 1975-10-14 | Solomon Aronovich Giller | Method for preparing N{HD 1{B -(2{40 -furanidyl)-and N{HD 1{B -2(2{40 -pyranidyl) uracils |
| US3960864A (en) * | 1974-05-06 | 1976-06-01 | The University Of Utah | Method of synthesizing 1-(tetrahydro-2-furanyl)-5-fluorouracil |
| DE2519079A1 (de) * | 1975-04-29 | 1976-11-11 | Inst Orch Sintesa Akademii Nau | Verfahren zur herstellung von n tief 1-(2'-furanicyl)-5-substituierten uracilen |
| JPS5259174A (en) * | 1975-11-10 | 1977-05-16 | Asahi Chem Ind Co Ltd | Preparation of n-substituted uracil compounds |
-
1976
- 1976-11-04 IE IE2461/76A patent/IE45046B1/en unknown
- 1976-11-05 GR GR52112A patent/GR62855B/el unknown
- 1976-11-05 CA CA265,062A patent/CA1122983A/en not_active Expired
- 1976-11-08 CH CH1402276A patent/CH616936A5/fr not_active IP Right Cessation
- 1976-11-12 GB GB47197/76A patent/GB1570219A/en not_active Expired
- 1976-11-15 FR FR7634249A patent/FR2332991A1/fr active Granted
- 1976-11-15 AU AU19655/76A patent/AU501833B2/en not_active Expired
- 1976-11-23 BE BE6045773A patent/BE848662A/xx not_active IP Right Cessation
- 1976-11-24 US US05/744,929 patent/US4249006A/en not_active Expired - Lifetime
- 1976-11-24 PT PT65883A patent/PT65883B/pt unknown
- 1976-11-24 PL PL1976193890A patent/PL104613B1/pl unknown
- 1976-11-24 DK DK528576AA patent/DK140635B/da not_active IP Right Cessation
- 1976-11-24 MX MX765150U patent/MX3873E/es unknown
- 1976-11-24 DE DE2653398A patent/DE2653398C2/de not_active Expired
- 1976-11-25 AT AT874876A patent/AT346858B/de not_active IP Right Cessation
- 1976-11-26 HU HU76TA1418A patent/HU176890B/hu unknown
- 1976-11-26 SE SE7613305A patent/SE423389B/xx not_active IP Right Cessation
- 1976-11-26 NO NO764048A patent/NO144887C/no unknown
- 1976-11-26 PH PH19171A patent/PH12998A/en unknown
- 1976-11-29 NL NL7613285A patent/NL7613285A/xx not_active Application Discontinuation
-
1983
- 1983-01-10 SG SG7/83A patent/SG783G/en unknown
- 1983-03-24 HK HK112/83A patent/HK11283A/xx unknown
-
1984
- 1984-12-30 MY MY88/84A patent/MY8400088A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SE423389B (sv) | 1982-05-03 |
| HU176890B (en) | 1981-05-28 |
| CH616936A5 (en, 2012) | 1980-04-30 |
| PT65883A (en) | 1976-12-01 |
| FR2332991A1 (fr) | 1977-06-24 |
| PL104613B1 (pl) | 1979-08-31 |
| NO144887C (no) | 1981-12-02 |
| SG783G (en) | 1983-09-09 |
| NO144887B (no) | 1981-08-24 |
| DE2653398A1 (de) | 1977-06-08 |
| SE7613305L (sv) | 1977-05-29 |
| DE2653398C2 (de) | 1986-07-17 |
| DK140635B (da) | 1979-10-15 |
| BE848662A (fr) | 1977-05-23 |
| AT346858B (de) | 1978-11-27 |
| GR62855B (en) | 1979-06-23 |
| IE45046B1 (en) | 1982-06-16 |
| PH12998A (en) | 1979-10-29 |
| HK11283A (en) | 1983-03-24 |
| IE45046L (en) | 1977-05-28 |
| CA1122983A (en) | 1982-05-04 |
| DK528576A (en, 2012) | 1977-05-29 |
| ATA874876A (de) | 1978-04-15 |
| MX3873E (es) | 1981-08-26 |
| NL7613285A (nl) | 1977-06-01 |
| MY8400088A (en) | 1984-12-31 |
| DK140635C (en, 2012) | 1980-03-10 |
| AU1965576A (en) | 1978-05-25 |
| AU501833B2 (en) | 1979-06-28 |
| FR2332991B1 (en, 2012) | 1980-03-21 |
| PT65883B (en) | 1978-10-12 |
| US4249006A (en) | 1981-02-03 |
| NO764048L (en, 2012) | 1977-06-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed [section 19, patents act 1949] | ||
| PCNP | Patent ceased through non-payment of renewal fee |