FI70026C - Foerfarande foer framstaellning av 4-ureido-oxazafosforiner - Google Patents
Foerfarande foer framstaellning av 4-ureido-oxazafosforiner Download PDFInfo
- Publication number
- FI70026C FI70026C FI812798A FI812798A FI70026C FI 70026 C FI70026 C FI 70026C FI 812798 A FI812798 A FI 812798A FI 812798 A FI812798 A FI 812798A FI 70026 C FI70026 C FI 70026C
- Authority
- FI
- Finland
- Prior art keywords
- hydrogen
- alkyl
- formula
- phenyl
- ethyl
- Prior art date
Links
- 238000005057 refrigeration Methods 0.000 title 1
- 239000001257 hydrogen Substances 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- -1 2-methanesulfonyloxyethyl Chemical group 0.000 claims description 15
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- ZTCOZLBXOHAWCA-UHFFFAOYSA-N NC(=O)NC1=PNOC=C1 Chemical class NC(=O)NC1=PNOC=C1 ZTCOZLBXOHAWCA-UHFFFAOYSA-N 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- DRAJWRKLRBNJRQ-UHFFFAOYSA-N Hydroxycarbamic acid Chemical class ONC(O)=O DRAJWRKLRBNJRQ-UHFFFAOYSA-N 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 239000012442 inert solvent Substances 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 239000007858 starting material Substances 0.000 claims description 4
- 229910052717 sulfur Chemical group 0.000 claims description 4
- 239000003377 acid catalyst Substances 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 150000002923 oximes Chemical class 0.000 claims description 3
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 125000004069 aziridinyl group Chemical group 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Chemical group O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 8
- 125000004433 nitrogen atom Chemical class N* 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 239000013078 crystal Substances 0.000 description 9
- GHTXIUJUEVFYHW-NYYWCZLTSA-N (ne)-n-[3-[amino-[bis(2-chloroethyl)amino]phosphoryl]oxypropylidene]hydroxylamine Chemical compound ClCCN(CCCl)P(=O)(N)OCC\C=N\O GHTXIUJUEVFYHW-NYYWCZLTSA-N 0.000 description 8
- 150000002431 hydrogen Chemical class 0.000 description 8
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- RANONBLIHMVXAJ-UHFFFAOYSA-N 4-hydroxycyclophosphamide Chemical compound OC1CCOP(=O)(N(CCCl)CCCl)N1 RANONBLIHMVXAJ-UHFFFAOYSA-N 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000004202 carbamide Substances 0.000 description 6
- 229960004397 cyclophosphamide Drugs 0.000 description 6
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 5
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical class NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 229960001330 hydroxycarbamide Drugs 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- KMUZEPMBBDHYBC-UHFFFAOYSA-N 2-(hydroxycarbamoylamino)acetic acid Chemical compound ONC(=O)NCC(O)=O KMUZEPMBBDHYBC-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 230000001085 cytostatic effect Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000013558 reference substance Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- IZJCEZHCNFRDKR-UHFFFAOYSA-N 4-ethoxy-2h-oxazaphosphinine Chemical compound CCOC1=PNOC=C1 IZJCEZHCNFRDKR-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- QTALEJBFHUYLPY-UHFFFAOYSA-N C(C)(=O)O.C(C1=CC=CC=C1)N=C=O Chemical compound C(C)(=O)O.C(C1=CC=CC=C1)N=C=O QTALEJBFHUYLPY-UHFFFAOYSA-N 0.000 description 2
- 102100035861 Cytosolic 5'-nucleotidase 1A Human genes 0.000 description 2
- 101000802744 Homo sapiens Cytosolic 5'-nucleotidase 1A Proteins 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- FLCMCTKYSHCVAJ-UHFFFAOYSA-N OC1=PNOC=C1 Chemical class OC1=PNOC=C1 FLCMCTKYSHCVAJ-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000000973 chemotherapeutic effect Effects 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 238000004809 thin layer chromatography Methods 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
- BOAAFIABUNHUDN-UHFFFAOYSA-N 1-(2-bromophenyl)-3-hydroxyurea Chemical compound ONC(=O)NC1=CC=CC=C1Br BOAAFIABUNHUDN-UHFFFAOYSA-N 0.000 description 1
- NEHSQHPPBUJKKZ-UHFFFAOYSA-N 1-[2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-yl]-1-hydroxyurea Chemical compound NC(=O)N(O)C1CCOP(=O)(N(CCCl)CCCl)N1 NEHSQHPPBUJKKZ-UHFFFAOYSA-N 0.000 description 1
- PJRWKVFIYLQKBV-UHFFFAOYSA-N 1-[2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-yl]-3-(9h-fluoren-2-yl)-1-hydroxyurea Chemical compound C=1C=C(C2=CC=CC=C2C2)C2=CC=1NC(=O)N(O)C1CCOP(=O)(N(CCCl)CCCl)N1 PJRWKVFIYLQKBV-UHFFFAOYSA-N 0.000 description 1
- SYEKKDBKUURZEG-UHFFFAOYSA-N 1-benzyl-3-hydroxyurea Chemical compound ONC(=O)NCC1=CC=CC=C1 SYEKKDBKUURZEG-UHFFFAOYSA-N 0.000 description 1
- CZQIJQFTRGDODI-UHFFFAOYSA-N 1-bromo-4-isocyanatobenzene Chemical compound BrC1=CC=C(N=C=O)C=C1 CZQIJQFTRGDODI-UHFFFAOYSA-N 0.000 description 1
- SXJYSIBLFGQAND-UHFFFAOYSA-N 1-isocyanato-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(N=C=O)=C1 SXJYSIBLFGQAND-UHFFFAOYSA-N 0.000 description 1
- GFNKTLQTQSALEJ-UHFFFAOYSA-N 1-isocyanato-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(N=C=O)C=C1 GFNKTLQTQSALEJ-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- KCCABKOTSYCLJI-UHFFFAOYSA-N 2-[[[2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-yl]-hydroxycarbamoyl]amino]acetate;cyclohexylazanium Chemical compound [NH3+]C1CCCCC1.[O-]C(=O)CNC(=O)N(O)C1CCOP(=O)(N(CCCl)CCCl)N1 KCCABKOTSYCLJI-UHFFFAOYSA-N 0.000 description 1
- RAXABQCFPAWRSY-UHFFFAOYSA-N 2-[bis(2-chloroethyl)amino]-3-(2-chloroethyl)-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-ol Chemical compound OC1CCOP(=O)(N(CCCl)CCCl)N1CCCl RAXABQCFPAWRSY-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- IGNOHILLSIWNMF-UHFFFAOYSA-N 3-benzyl-1-[2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-yl]-1-hydroxyurea Chemical compound C=1C=CC=CC=1CNC(=O)N(O)C1CCOP(=O)(N(CCCl)CCCl)N1 IGNOHILLSIWNMF-UHFFFAOYSA-N 0.000 description 1
- ZSJQOUZCZSWXAM-UHFFFAOYSA-N 7,9-dihydro-3h-purine-2,6,8-trione;hydrochloride Chemical class Cl.N1C(=O)NC(=O)C2=C1NC(=O)N2 ZSJQOUZCZSWXAM-UHFFFAOYSA-N 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- JYCULSYEFRCGNR-UHFFFAOYSA-N O=P1OC=CC=N1 Chemical compound O=P1OC=CC=N1 JYCULSYEFRCGNR-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- LURYMYITPCOQAU-UHFFFAOYSA-N benzoyl isocyanate Chemical compound O=C=NC(=O)C1=CC=CC=C1 LURYMYITPCOQAU-UHFFFAOYSA-N 0.000 description 1
- VLQHNAMRWPQWNK-UHFFFAOYSA-N benzyl 2-aminoacetate;hydron;chloride Chemical compound Cl.NCC(=O)OCC1=CC=CC=C1 VLQHNAMRWPQWNK-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- KQWGXHWJMSMDJJ-UHFFFAOYSA-N cyclohexyl isocyanate Chemical compound O=C=NC1CCCCC1 KQWGXHWJMSMDJJ-UHFFFAOYSA-N 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000001867 hydroperoxy group Chemical group [*]OO[H] 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- VFKUVJKBMUOOQX-UHFFFAOYSA-N n-hydroxymorpholine-4-carboxamide Chemical compound ONC(=O)N1CCOCC1 VFKUVJKBMUOOQX-UHFFFAOYSA-N 0.000 description 1
- 150000002829 nitrogen Chemical class 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 231100000927 organotoxic Toxicity 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 229960000875 trofosfamide Drugs 0.000 description 1
- UMKFEPPTGMDVMI-UHFFFAOYSA-N trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
- C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
- C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
- C07F9/65846—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring the phosphorus atom being part of a six-membered ring which may be condensed with another ring system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Claims (3)
1. Förfarande för framställning av farmakologiskt aktiva 4-ureido-oxaza-fosforiner med den allmänna formeln I OH X ' Il /6 R N - C - N 1 „UR4 "R7 N x .H X ' X X I Rn , P X" R. 2 x . X 4 r o ...___R o u 7^ 4 R 4 och deras farmakologiskt lämpliga salter, i vilken formel X är syre eller svavel, , R2 och , som kan vara lika eller olika betecknar väte, metyl, etyl, 2-kloretyl eller 2-metansulfonyloxietyl, resterna R^ som kan vara lika eller olika, betecknar väte, metyl eller etyl, Rg är väte, C^^-alkyl, hydroxi- C^_4-alkyl eller fenyl, och R7 är väte, karbamoyl eller ' s 8 -OR , där R är väte, C^_4~alkyl, fenyl eller bensyl, eller en rak eller förgrenad alkyl med 1-18 kolatomer, varvid alkylresten kan innehälla 1-3 likadana eller olika 9 substituenter av följande: -OH, -halogen, -COOH, -COOR , -CONH^ , fenyl, bensyloxikarbonylrest, -N(R9)2, (R9) ^ , -OR9, -SR9, -SO-R9, -S02~R9, -s03H eller -PO(CH2)2, där R9 betecknar metyl eller etyl, eller R? är en fenyl-C1 _4~alkylrest som möjligen kan vara substituerad med 1 eller 2 karboxigrupper vid restens fenyl- och/eller alkyldel, allyl eller cykloalkyl med 3-8 kolatomer eller tetrahvdrofuranyl, eller tetrahydropyranyl eller fenyl, som kan vara osubstituerad eller som kan ha en eller tvä substituenter säsom C^_4~alkyl, C^_2~alkoxi, nitro, halogen, trifluorometyl, -S02NH2, karboxi, bensyloxikarbonyl och/eller karh-C^ _4~alkoxi, eller bensyl eller 70026 benshydryl eller naftyl eller fluorenyl eller pyridyl eller tienyl eller bensoyl eller C1_^-alkanoyl eller R6 och tillsammans med atomer, till vilka de är bundna, utgör en del av ett mättat heterocykliskt ringsystem som dessutom kan innehälla en syreatom, en lägrealkylsubstituerad kväve- atom eller sä kan den innehälla en svavelatom av typ -S-, -SO- eller -SO„, eller R^ och R_ bildar en del av en osubsti-Z 6 7 tuerad eller en cyano- eller karbamoylsubstituerad aziridinring, kännetecknat av att a) 4-hydroxi- eller 4-metoxi- eller 4-etoxioxazafosforin med den allnänna formeln II R1 f 3 OY >, > S 2 /^p, / 11 o ' -o------/R4R4 R4 där R^, R^/ R^ och R^ har sauma betydelse som i formel I och Y är väte, metyl eller etyl, omsättes med hydroxikarbamat-de rivat med den allmänna formeln III X R, n / 6 HO - NH - C - N III \ R7 där X betyder detsamma som i formel I, i ett inert lösningsmedel, eventuellt med nedkylning eller uppvärmning och/eller eventuellt i närvaro av en sur katalysator, eller att b) en oxim med den allmänna formeln IV R1 R3 / \ / NH R, ,P
2 X \
0 O- C - CH C - N - OH IV / \ 1 I R4 R4 R4 R4
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8029222 | 1980-09-10 | ||
| GB8029222 | 1980-09-10 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI812798L FI812798L (fi) | 1982-03-11 |
| FI70026B FI70026B (fi) | 1986-01-31 |
| FI70026C true FI70026C (fi) | 1986-09-12 |
Family
ID=10515985
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI812798A FI70026C (fi) | 1980-09-10 | 1981-09-09 | Foerfarande foer framstaellning av 4-ureido-oxazafosforiner |
Country Status (29)
| Country | Link |
|---|---|
| JP (1) | JPS5785396A (sv) |
| AR (1) | AR231989A1 (sv) |
| AT (1) | AT386210B (sv) |
| AU (1) | AU538275B2 (sv) |
| BE (1) | BE890276A (sv) |
| CA (2) | CA1161453A (sv) |
| CH (1) | CH650787A5 (sv) |
| CS (1) | CS227680B2 (sv) |
| DD (1) | DD202166A5 (sv) |
| DE (1) | DE3133309A1 (sv) |
| DK (1) | DK400481A (sv) |
| EG (1) | EG15392A (sv) |
| ES (1) | ES505324A0 (sv) |
| FI (1) | FI70026C (sv) |
| FR (1) | FR2489825A1 (sv) |
| GR (1) | GR75300B (sv) |
| HU (1) | HU185953B (sv) |
| IE (1) | IE51784B1 (sv) |
| IL (1) | IL63661A (sv) |
| IT (2) | IT1198350B (sv) |
| LU (1) | LU83613A1 (sv) |
| NL (1) | NL8104093A (sv) |
| NO (1) | NO161261C (sv) |
| PL (1) | PL128627B1 (sv) |
| PT (1) | PT73645B (sv) |
| RO (1) | RO83972B (sv) |
| SE (1) | SE458203B (sv) |
| YU (1) | YU42584B (sv) |
| ZA (1) | ZA815922B (sv) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3569737D1 (en) * | 1984-03-01 | 1989-06-01 | Asta Pharma Ag | Salts of oxazaphosphorine derivatives |
| ZA851062B (en) * | 1984-03-01 | 1985-11-27 | Asta Werke Ag Chem Fab | Salts of oxazaphosphorine derivatives and process for their production |
| WO2016089208A2 (en) | 2014-12-04 | 2016-06-09 | Stichting Maastricht Radiation Oncology "Maastro-Clinic" | Sulfonamide, sulfamate and sulfamide derivatives of anti-cancer agents |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA955937A (en) * | 1971-06-28 | 1974-10-08 | Shionogi And Co. Ltd. | Cyclic phosphamide derivatives |
| US3911005A (en) * | 1974-09-12 | 1975-10-07 | Monsanto Co | 1,3,2-Diazaphospholidine compounds |
| JPS5159886A (sv) * | 1974-11-20 | 1976-05-25 | Shionogi Seiyaku Kk |
-
1981
- 1981-08-22 DE DE19813133309 patent/DE3133309A1/de active Granted
- 1981-08-25 IE IE1951/81A patent/IE51784B1/en unknown
- 1981-08-26 ZA ZA815922A patent/ZA815922B/xx unknown
- 1981-08-26 IL IL63661A patent/IL63661A/xx not_active IP Right Cessation
- 1981-08-26 AU AU74657/81A patent/AU538275B2/en not_active Ceased
- 1981-08-31 CH CH5584/81A patent/CH650787A5/de not_active IP Right Cessation
- 1981-08-31 GR GR65896A patent/GR75300B/el unknown
- 1981-09-03 NL NL8104093A patent/NL8104093A/xx not_active Application Discontinuation
- 1981-09-04 CS CS816537A patent/CS227680B2/cs unknown
- 1981-09-07 LU LU83613A patent/LU83613A1/de unknown
- 1981-09-07 AT AT0386481A patent/AT386210B/de not_active IP Right Cessation
- 1981-09-08 HU HU812580A patent/HU185953B/hu unknown
- 1981-09-08 FR FR8116999A patent/FR2489825A1/fr active Granted
- 1981-09-08 SE SE8105340A patent/SE458203B/sv not_active IP Right Cessation
- 1981-09-08 EG EG508/81A patent/EG15392A/xx active
- 1981-09-08 DD DD81233132A patent/DD202166A5/de unknown
- 1981-09-08 RO RO105257A patent/RO83972B/ro unknown
- 1981-09-09 FI FI812798A patent/FI70026C/fi not_active IP Right Cessation
- 1981-09-09 NO NO813063A patent/NO161261C/no unknown
- 1981-09-09 CA CA000385516A patent/CA1161453A/en not_active Expired
- 1981-09-09 IT IT23860/81A patent/IT1198350B/it active
- 1981-09-09 PT PT73645A patent/PT73645B/pt unknown
- 1981-09-09 DK DK400481A patent/DK400481A/da not_active Application Discontinuation
- 1981-09-09 BE BE2/59345A patent/BE890276A/fr not_active IP Right Cessation
- 1981-09-09 JP JP56141108A patent/JPS5785396A/ja active Granted
- 1981-09-09 PL PL1981232960A patent/PL128627B1/pl unknown
- 1981-09-09 ES ES505324A patent/ES505324A0/es active Granted
- 1981-09-10 AR AR286736A patent/AR231989A1/es active
- 1981-09-10 YU YU2179/81A patent/YU42584B/xx unknown
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1984
- 1984-05-30 CA CA000455507A patent/CA1184563B/en not_active Expired
- 1984-06-12 IT IT21372/84A patent/IT1220985B/it active
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| MM | Patent lapsed |
Owner name: ASTA-WERKE AKTIENGESELLSCHAFT |