DE3234917A1 - Verfahren zur herstellung von n(pfeil hoch)6(pfeil hoch),9-disubstituierten adeninen - Google Patents
Verfahren zur herstellung von n(pfeil hoch)6(pfeil hoch),9-disubstituierten adeninenInfo
- Publication number
- DE3234917A1 DE3234917A1 DE19823234917 DE3234917A DE3234917A1 DE 3234917 A1 DE3234917 A1 DE 3234917A1 DE 19823234917 DE19823234917 DE 19823234917 DE 3234917 A DE3234917 A DE 3234917A DE 3234917 A1 DE3234917 A1 DE 3234917A1
- Authority
- DE
- Germany
- Prior art keywords
- general formula
- reaction
- adenine
- carbon atoms
- phase change
- 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
- 238000004519 manufacturing process Methods 0.000 title description 9
- -1 N, 9-disubstituted adenine Chemical class 0.000 claims description 75
- 238000000034 method Methods 0.000 claims description 67
- 238000006243 chemical reaction Methods 0.000 claims description 52
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 41
- 239000003054 catalyst Substances 0.000 claims description 38
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 32
- 229930024421 Adenine Natural products 0.000 claims description 31
- 229960000643 adenine Drugs 0.000 claims description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 29
- 229910052751 metal Inorganic materials 0.000 claims description 28
- 239000002184 metal Substances 0.000 claims description 28
- 230000008859 change Effects 0.000 claims description 27
- 230000008569 process Effects 0.000 claims description 25
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 20
- 229920001223 polyethylene glycol Polymers 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 14
- 239000002202 Polyethylene glycol Substances 0.000 claims description 13
- 229960000583 acetic acid Drugs 0.000 claims description 13
- 150000005215 alkyl ethers Chemical class 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 239000002244 precipitate Substances 0.000 claims description 9
- 239000007795 chemical reaction product Substances 0.000 claims description 7
- 239000012362 glacial acetic acid Substances 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 150000001340 alkali metals Chemical class 0.000 claims description 4
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 150000002431 hydrogen Chemical group 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 239000011541 reaction mixture Substances 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 239000002841 Lewis acid Chemical class 0.000 claims description 3
- 239000007810 chemical reaction solvent Substances 0.000 claims description 3
- 125000002425 furfuryl group Chemical group C(C1=CC=CO1)* 0.000 claims description 3
- 150000007517 lewis acids Chemical class 0.000 claims description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical class OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 150000003863 ammonium salts Chemical class 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 150000007514 bases Chemical class 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052736 halogen Chemical group 0.000 claims description 2
- 150000002367 halogens Chemical group 0.000 claims description 2
- 229910000039 hydrogen halide Inorganic materials 0.000 claims description 2
- 239000012433 hydrogen halide Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 238000011065 in-situ storage Methods 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 29
- 239000013078 crystal Substances 0.000 description 22
- CKOMXBHMKXXTNW-UHFFFAOYSA-N 6-methyladenine Chemical compound CNC1=NC=NC2=C1N=CN2 CKOMXBHMKXXTNW-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- 239000000203 mixture Substances 0.000 description 19
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 11
- 238000004821 distillation Methods 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 238000004140 cleaning Methods 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- MJGOLNNLNQQIHR-UHFFFAOYSA-N 1-chloro-2-(chloromethyl)-3-fluorobenzene Chemical compound FC1=CC=CC(Cl)=C1CCl MJGOLNNLNQQIHR-UHFFFAOYSA-N 0.000 description 6
- 230000029936 alkylation Effects 0.000 description 6
- 238000005804 alkylation reaction Methods 0.000 description 6
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 6
- ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical compound ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 5
- VAEPQHITLRNBPM-UHFFFAOYSA-N 9-[(2-chloro-6-fluorophenyl)methyl]-n-methylpurin-6-amine Chemical compound C1=NC=2C(NC)=NC=NC=2N1CC1=C(F)C=CC=C1Cl VAEPQHITLRNBPM-UHFFFAOYSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 229940124536 anticoccidial agent Drugs 0.000 description 5
- 239000003224 coccidiostatic agent Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- BVIAOQMSVZHOJM-UHFFFAOYSA-N N(6),N(6)-dimethyladenine Chemical compound CN(C)C1=NC=NC2=C1N=CN2 BVIAOQMSVZHOJM-UHFFFAOYSA-N 0.000 description 4
- 238000000862 absorption spectrum Methods 0.000 description 4
- 239000003377 acid catalyst Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 4
- JIKRBGNBOGLWPV-UHFFFAOYSA-N n-methyl-7h-purin-6-amine;sodium Chemical compound [Na].CNC1=NC=NC2=C1NC=N2 JIKRBGNBOGLWPV-UHFFFAOYSA-N 0.000 description 4
- CIAUYDNALIJKPK-UHFFFAOYSA-N n-propyl-7h-purin-6-amine Chemical compound CCCNC1=NC=NC2=C1NC=N2 CIAUYDNALIJKPK-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 150000004714 phosphonium salts Chemical class 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- LBOBESSDSGODDD-UHFFFAOYSA-N 1,3-dichloro-2-(chloromethyl)benzene Chemical compound ClCC1=C(Cl)C=CC=C1Cl LBOBESSDSGODDD-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Natural products CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 150000003983 crown ethers Chemical class 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- 229910000000 metal hydroxide Inorganic materials 0.000 description 2
- 150000004692 metal hydroxides Chemical class 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 1
- PDFGFQUSSYSWNI-UHFFFAOYSA-N 2-(bromomethyl)-1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1CBr PDFGFQUSSYSWNI-UHFFFAOYSA-N 0.000 description 1
- IGUVNNXFTDCASP-UHFFFAOYSA-N 2-(bromomethyl)-1-chloro-3-fluorobenzene Chemical compound FC1=CC=CC(Cl)=C1CBr IGUVNNXFTDCASP-UHFFFAOYSA-N 0.000 description 1
- JBMBVWROWJGFMG-UHFFFAOYSA-N 2-chloro-7h-purine Chemical compound ClC1=NC=C2NC=NC2=N1 JBMBVWROWJGFMG-UHFFFAOYSA-N 0.000 description 1
- SMADWRYCYBUIKH-UHFFFAOYSA-N 2-methyl-7h-purin-6-amine Chemical compound CC1=NC(N)=C2NC=NC2=N1 SMADWRYCYBUIKH-UHFFFAOYSA-N 0.000 description 1
- USCCECGPGBGFOM-UHFFFAOYSA-N 2-propyl-7h-purin-6-amine Chemical compound CCCC1=NC(N)=C2NC=NC2=N1 USCCECGPGBGFOM-UHFFFAOYSA-N 0.000 description 1
- UIJIQXGRFSPYQW-UHFFFAOYSA-N 6-methylthiopurine Chemical compound CSC1=NC=NC2=C1N=CN2 UIJIQXGRFSPYQW-UHFFFAOYSA-N 0.000 description 1
- JVYXLOBVPSJRKI-UHFFFAOYSA-N 9-[(2,6-dichlorophenyl)methyl]-n-methylpurin-6-amine Chemical compound C1=NC=2C(NC)=NC=NC=2N1CC1=C(Cl)C=CC=C1Cl JVYXLOBVPSJRKI-UHFFFAOYSA-N 0.000 description 1
- QUWRDAYNMYKWRG-UHFFFAOYSA-N 9-[(2,6-dichlorophenyl)methyl]-n-propylpurin-6-amine Chemical compound C1=NC=2C(NCCC)=NC=NC=2N1CC1=C(Cl)C=CC=C1Cl QUWRDAYNMYKWRG-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241001432959 Chernes Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- NWBJYWHLCVSVIJ-UHFFFAOYSA-N N-benzyladenine Chemical compound N=1C=NC=2NC=NC=2C=1NCC1=CC=CC=C1 NWBJYWHLCVSVIJ-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000000538 analytical sample Substances 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 150000003974 aralkylamines Chemical class 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- 159000000009 barium salts Chemical class 0.000 description 1
- ZUDYPQRUOYEARG-UHFFFAOYSA-L barium(2+);dihydroxide;octahydrate Chemical compound O.O.O.O.O.O.O.O.[OH-].[OH-].[Ba+2] ZUDYPQRUOYEARG-UHFFFAOYSA-L 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 150000001983 dialkylethers Chemical class 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 125000000118 dimethyl group Chemical class [H]C([H])([H])* 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000004175 fluorobenzyl group Chemical group 0.000 description 1
- DDRPCXLAQZKBJP-UHFFFAOYSA-N furfurylamine Chemical compound NCC1=CC=CO1 DDRPCXLAQZKBJP-UHFFFAOYSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- BICAGYDGRXJYGD-UHFFFAOYSA-N hydrobromide;hydrochloride Chemical compound Cl.Br BICAGYDGRXJYGD-UHFFFAOYSA-N 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- HPZMWTNATZPBIH-UHFFFAOYSA-N methyl adenine Natural products CN1C=NC2=NC=NC2=C1N HPZMWTNATZPBIH-UHFFFAOYSA-N 0.000 description 1
- STYFLCAHEVROJU-UHFFFAOYSA-N n,n-diethyl-7h-purin-6-amine Chemical class CCN(CC)C1=NC=NC2=C1NC=N2 STYFLCAHEVROJU-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- 229940113116 polyethylene glycol 1000 Drugs 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229940057847 polyethylene glycol 600 Drugs 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 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)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14956781A JPS5852288A (ja) | 1981-09-24 | 1981-09-24 | ６−置換アデニンの製造法 |
| JP56153878A JPS5857381A (ja) | 1981-09-30 | 1981-09-30 | Ｎ６，９−ジ置換アデニン誘導体の製造法 |
| JP15486281A JPS5857382A (ja) | 1981-10-01 | 1981-10-01 | Ｎ↑６，９−ジ置換アデニンの精製法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3234917A1 true DE3234917A1 (de) | 1983-04-07 |
| DE3234917C2 DE3234917C2 (en, 2012) | 1992-06-17 |
Family
ID=27319784
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19823234917 Granted DE3234917A1 (de) | 1981-09-24 | 1982-09-21 | Verfahren zur herstellung von n(pfeil hoch)6(pfeil hoch),9-disubstituierten adeninen |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US4900826A (en, 2012) |
| CH (1) | CH655113A5 (en, 2012) |
| DE (1) | DE3234917A1 (en, 2012) |
| DK (1) | DK151259C (en, 2012) |
| ES (1) | ES8403486A1 (en, 2012) |
| FR (1) | FR2513254B1 (en, 2012) |
| GB (1) | GB2109370B (en, 2012) |
| NL (1) | NL8203718A (en, 2012) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8408615D0 (en) * | 1984-04-04 | 1984-05-16 | Wellcome Found | Heterocyclic compounds |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4100159A (en) * | 1977-02-07 | 1978-07-11 | Merck & Co., Inc. | Process for preparation of 9-(2,6-dihalobenzyl)adenines |
| US4189485A (en) * | 1977-08-23 | 1980-02-19 | Takeda Chemical Industries, Ltd. | Purine derivatives |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI64596C (fi) * | 1977-02-07 | 1983-12-12 | Merck & Co Inc | Foerfarande foer framstaellning av 9-(2,6-dihalogenbensyl)adenin vaesentligen fri fraon 3-isomeren |
| JPS5844084B2 (ja) * | 1977-04-01 | 1983-09-30 | 住友化学工業株式会社 | イオン性プルランゲルの製造法 |
-
1982
- 1982-09-17 US US06/419,317 patent/US4900826A/en not_active Expired - Lifetime
- 1982-09-21 DE DE19823234917 patent/DE3234917A1/de active Granted
- 1982-09-23 GB GB08227129A patent/GB2109370B/en not_active Expired
- 1982-09-23 DK DK423282A patent/DK151259C/da not_active IP Right Cessation
- 1982-09-23 CH CH5636/82A patent/CH655113A5/de not_active IP Right Cessation
- 1982-09-23 ES ES515903A patent/ES8403486A1/es not_active Expired
- 1982-09-24 FR FR8216167A patent/FR2513254B1/fr not_active Expired
- 1982-09-24 NL NL8203718A patent/NL8203718A/nl not_active Application Discontinuation
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4100159A (en) * | 1977-02-07 | 1978-07-11 | Merck & Co., Inc. | Process for preparation of 9-(2,6-dihalobenzyl)adenines |
| US4189485A (en) * | 1977-08-23 | 1980-02-19 | Takeda Chemical Industries, Ltd. | Purine derivatives |
Non-Patent Citations (1)
| Title |
|---|
| J. Am. Chem. Soc. 82, 1960, 3971 * |
Also Published As
| Publication number | Publication date |
|---|---|
| NL8203718A (nl) | 1983-04-18 |
| ES515903A0 (es) | 1984-03-16 |
| GB2109370A (en) | 1983-06-02 |
| FR2513254A1 (fr) | 1983-03-25 |
| DK423282A (da) | 1983-03-25 |
| ES8403486A1 (es) | 1984-03-16 |
| FR2513254B1 (fr) | 1987-04-30 |
| CH655113A5 (de) | 1986-03-27 |
| DK151259B (da) | 1987-11-16 |
| DE3234917C2 (en, 2012) | 1992-06-17 |
| US4900826A (en) | 1990-02-13 |
| GB2109370B (en) | 1986-01-22 |
| DK151259C (da) | 1988-05-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8128 | New person/name/address of the agent |
Representative=s name: TUERK, D., DIPL.-CHEM. DR.RER.NAT. GILLE, C., DIPL |
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| 8110 | Request for examination paragraph 44 | ||
| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition |