DE1935027A1 - Verfahren zur Herstellung von 1-Glykosyl-5-azacytosinen - Google Patents
Verfahren zur Herstellung von 1-Glykosyl-5-azacytosinenInfo
- Publication number
- DE1935027A1 DE1935027A1 DE19691935027 DE1935027A DE1935027A1 DE 1935027 A1 DE1935027 A1 DE 1935027A1 DE 19691935027 DE19691935027 DE 19691935027 DE 1935027 A DE1935027 A DE 1935027A DE 1935027 A1 DE1935027 A1 DE 1935027A1
- Authority
- DE
- Germany
- Prior art keywords
- carbon atoms
- general formula
- advantageously
- methanol
- glycosyl
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 238000006136 alcoholysis reaction Methods 0.000 claims description 5
- 229910021529 ammonia Inorganic materials 0.000 claims description 5
- 238000005915 ammonolysis reaction Methods 0.000 claims description 5
- 239000012948 isocyanate Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- 239000012442 inert solvent Substances 0.000 claims description 4
- 150000002513 isocyanates Chemical class 0.000 claims description 4
- -1 alkali metal alkoxides Chemical class 0.000 claims description 3
- 125000003147 glycosyl group Chemical group 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 238000006140 methanolysis reaction Methods 0.000 claims description 3
- 239000002808 molecular sieve Substances 0.000 claims description 3
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims 1
- 229960002756 azacitidine Drugs 0.000 description 7
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-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
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- VKJMPYGLTDMUPZ-UHFFFAOYSA-N 5-amino-1h-triazin-6-one Chemical class NC1=CN=NNC1=O VKJMPYGLTDMUPZ-UHFFFAOYSA-N 0.000 description 1
- XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 description 1
- SQSPRWMERUQXNE-UHFFFAOYSA-N Guanylurea Chemical compound NC(=N)NC(N)=O SQSPRWMERUQXNE-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 230000000719 anti-leukaemic effect Effects 0.000 description 1
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 1
- MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- OHJMTUPIZMNBFR-UHFFFAOYSA-N biuret Chemical class NC(=O)NC(N)=O OHJMTUPIZMNBFR-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 150000002357 guanidines Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- XEBPBJPZBUSUEO-UHFFFAOYSA-N n-(diaminomethylidene)formamide Chemical compound NC(=N)NC=O XEBPBJPZBUSUEO-UHFFFAOYSA-N 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/12—Triazine radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Gripping On Spindles (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS770868 | 1968-11-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1935027A1 true DE1935027A1 (de) | 1970-06-04 |
Family
ID=5426669
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19691935027 Pending DE1935027A1 (de) | 1968-11-12 | 1969-07-10 | Verfahren zur Herstellung von 1-Glykosyl-5-azacytosinen |
Country Status (12)
| Country | Link |
|---|---|
| AT (1) | AT292205B (enExample) |
| BE (1) | BE732796A (enExample) |
| CH (1) | CH507969A (enExample) |
| DE (1) | DE1935027A1 (enExample) |
| DK (1) | DK128008B (enExample) |
| ES (1) | ES367451A1 (enExample) |
| FR (1) | FR2023018A1 (enExample) |
| GB (1) | GB1227692A (enExample) |
| IT (1) | IT1033029B (enExample) |
| NL (1) | NL6907961A (enExample) |
| NO (1) | NO126626B (enExample) |
| SE (1) | SE350048B (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2012888C3 (de) * | 1970-03-14 | 1981-04-02 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Verfahren zur Herstellung von 5-Azapyrimidinnucleosiden |
| US7038038B2 (en) | 2003-03-17 | 2006-05-02 | Pharmion Corporation | Synthesis of 5-azacytidine |
| US6887855B2 (en) | 2003-03-17 | 2005-05-03 | Pharmion Corporation | Forms of 5-azacytidine |
| US6943249B2 (en) | 2003-03-17 | 2005-09-13 | Ash Stevens, Inc. | Methods for isolating crystalline Form I of 5-azacytidine |
| ES2774226T3 (es) | 2008-05-15 | 2020-07-17 | Celgene Corp | Formulaciones orales de análogos de citidina y métodos de uso de los mismos |
| US9951098B2 (en) | 2011-03-31 | 2018-04-24 | Pharmion Llc | Synthesis of 5-azacytidine |
-
1969
- 1969-04-24 CH CH624769A patent/CH507969A/de not_active IP Right Cessation
- 1969-05-06 NO NO185469A patent/NO126626B/no unknown
- 1969-05-08 GB GB1227692D patent/GB1227692A/en not_active Expired
- 1969-05-08 AT AT440869A patent/AT292205B/de not_active IP Right Cessation
- 1969-05-09 BE BE732796D patent/BE732796A/xx unknown
- 1969-05-13 SE SE681169A patent/SE350048B/xx unknown
- 1969-05-20 ES ES367451A patent/ES367451A1/es not_active Expired
- 1969-05-23 NL NL6907961A patent/NL6907961A/xx unknown
- 1969-05-30 DK DK292969A patent/DK128008B/da unknown
- 1969-06-20 FR FR6920666A patent/FR2023018A1/fr not_active Withdrawn
- 1969-07-04 IT IT1919969A patent/IT1033029B/it active
- 1969-07-10 DE DE19691935027 patent/DE1935027A1/de active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DK128008B (da) | 1974-02-18 |
| IT1033029B (it) | 1979-07-10 |
| BE732796A (enExample) | 1969-10-16 |
| SE350048B (enExample) | 1972-10-16 |
| FR2023018A1 (enExample) | 1970-08-07 |
| CH507969A (de) | 1971-05-31 |
| GB1227692A (enExample) | 1971-04-07 |
| NL6907961A (enExample) | 1970-05-14 |
| AT292205B (de) | 1971-08-25 |
| ES367451A1 (es) | 1971-04-01 |
| NO126626B (enExample) | 1973-03-05 |
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