DE1645921C3 - 2-Oxo-13,2-osazaphosphorinane, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate - Google Patents
2-Oxo-13,2-osazaphosphorinane, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische PräparateInfo
- Publication number
- DE1645921C3 DE1645921C3 DE1966A0052989 DEA0052989A DE1645921C3 DE 1645921 C3 DE1645921 C3 DE 1645921C3 DE 1966A0052989 DE1966A0052989 DE 1966A0052989 DE A0052989 A DEA0052989 A DE A0052989A DE 1645921 C3 DE1645921 C3 DE 1645921C3
- Authority
- DE
- Germany
- Prior art keywords
- chloroethyl
- solution
- oxo
- ether
- oxazaphosphorinane
- 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 description 9
- 239000000825 pharmaceutical preparation Substances 0.000 title description 2
- 238000002360 preparation method Methods 0.000 title 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 76
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 71
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
- 239000000243 solution Substances 0.000 description 53
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 25
- -1 3-chloropropyl radical Chemical class 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- 238000001816 cooling Methods 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- 238000003756 stirring Methods 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 15
- 239000003610 charcoal Substances 0.000 description 12
- 238000009835 boiling Methods 0.000 description 11
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 239000012452 mother liquor Substances 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 125000005843 halogen group Chemical group 0.000 description 7
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- GLZNEMWJNDMRFW-UHFFFAOYSA-N bis(2-chloroethyl)aminophosphonic acid dihydrochloride Chemical compound Cl.Cl.ClCCN(P(O)(=O)O)CCCl GLZNEMWJNDMRFW-UHFFFAOYSA-N 0.000 description 4
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- SBMJSKYKTAAHAB-UHFFFAOYSA-N 2-chloro-3-(2-chloroethyl)-1,3,2$l^{5}-oxazaphosphinane 2-oxide Chemical compound ClCCN1CCCOP1(Cl)=O SBMJSKYKTAAHAB-UHFFFAOYSA-N 0.000 description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 3
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical compound [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- MRIMWDXKBILRPB-UHFFFAOYSA-N O=P1NCCCO1 Chemical compound O=P1NCCCO1 MRIMWDXKBILRPB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- IQPMYTNILJQKBS-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)-n-dichlorophosphorylethanamine Chemical compound ClCCN(P(Cl)(Cl)=O)CCCl IQPMYTNILJQKBS-UHFFFAOYSA-N 0.000 description 2
- UBRSKPGONDTDNE-UHFFFAOYSA-N 3-(2-chloroethylamino)propan-1-ol;hydrochloride Chemical compound Cl.OCCCNCCCl UBRSKPGONDTDNE-UHFFFAOYSA-N 0.000 description 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 2
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical group C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- GYIGCNQZHHSGFA-UHFFFAOYSA-N NP(O)(O)=O.Cl.Cl Chemical compound NP(O)(O)=O.Cl.Cl GYIGCNQZHHSGFA-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- TXFLGZOGNOOEFZ-UHFFFAOYSA-N bis(2-chloroethyl)amine Chemical compound ClCCNCCCl TXFLGZOGNOOEFZ-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000001085 cytostatic effect Effects 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 229940050176 methyl chloride Drugs 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical compound NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- COQYINRSUYJILQ-UHFFFAOYSA-N 1-(aziridin-1-yl)propan-1-ol Chemical compound CCC(O)N1CC1 COQYINRSUYJILQ-UHFFFAOYSA-N 0.000 description 1
- ZIXPOIOWMASQOC-UHFFFAOYSA-N 2-(aziridin-1-yl)-3-(2-chloroethyl)-1,3,2$l^{5}-oxazaphosphinane 2-oxide Chemical compound ClCCN1CCCOP1(=O)N1CC1 ZIXPOIOWMASQOC-UHFFFAOYSA-N 0.000 description 1
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- MVHLGZMCYAPSCZ-UHFFFAOYSA-N CC(C)(CN1CCCl)COP1(N(CCCl)CCCl)=O Chemical compound CC(C)(CN1CCCl)COP1(N(CCCl)CCCl)=O MVHLGZMCYAPSCZ-UHFFFAOYSA-N 0.000 description 1
- FMOLYPLOKRFKHR-UHFFFAOYSA-N CC(CCN1CCCl)OP1(N(CCCl)CCCl)=O Chemical compound CC(CCN1CCCl)OP1(N(CCCl)CCCl)=O FMOLYPLOKRFKHR-UHFFFAOYSA-N 0.000 description 1
- AUMFFMKSRXJICI-UHFFFAOYSA-N CC(CCO1)N(CCCl)P1(Cl)=O Chemical compound CC(CCO1)N(CCCl)P1(Cl)=O AUMFFMKSRXJICI-UHFFFAOYSA-N 0.000 description 1
- PZSLRBIMYCGJHS-UHFFFAOYSA-N CCCC(CCN1CCCl)OP1(NCCCl)=O Chemical compound CCCC(CCN1CCCl)OP1(NCCCl)=O PZSLRBIMYCGJHS-UHFFFAOYSA-N 0.000 description 1
- GTXMEZUSXBSOME-UHFFFAOYSA-N CN(CCCl)P(O)(O)=O.Cl.Cl Chemical compound CN(CCCl)P(O)(O)=O.Cl.Cl GTXMEZUSXBSOME-UHFFFAOYSA-N 0.000 description 1
- FMWFLWKJZMQPFX-UHFFFAOYSA-N CN(CCCl)P1(OCCCN1CCCO)=O Chemical compound CN(CCCl)P1(OCCCN1CCCO)=O FMWFLWKJZMQPFX-UHFFFAOYSA-N 0.000 description 1
- YWZQTGXMHBSRGB-UHFFFAOYSA-N CN(CCCl)P1(OCCCN1CCCl)=O Chemical compound CN(CCCl)P1(OCCCN1CCCl)=O YWZQTGXMHBSRGB-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- VUVFECZJSWRIAQ-UHFFFAOYSA-N ClP1(OC(CCN1CCCl)C)=O Chemical compound ClP1(OC(CCN1CCCl)C)=O VUVFECZJSWRIAQ-UHFFFAOYSA-N 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- SBUYUOWLACJEJU-UHFFFAOYSA-N O=P1(N(CCCl)CCCl)OCCCN1CCCCl Chemical compound O=P1(N(CCCl)CCCl)OCCCN1CCCCl SBUYUOWLACJEJU-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 208000001792 Sarcoma 37 Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- JLJCKJXTAZLJMO-UHFFFAOYSA-N [N].ClC(Cl)Cl Chemical compound [N].ClC(Cl)Cl JLJCKJXTAZLJMO-UHFFFAOYSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 150000003015 phosphoric acid halides Chemical class 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- UMKFEPPTGMDVMI-UHFFFAOYSA-N trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (22)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1966A0052989 DE1645921C3 (de) | 1966-07-11 | 1966-07-11 | 2-Oxo-13,2-osazaphosphorinane, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate |
| LU53924D LU53924A1 (fi) | 1966-07-11 | 1967-06-20 | |
| PL1967151888A PL81415B1 (fi) | 1966-07-11 | 1967-06-22 | |
| AT597767A AT274001B (de) | 1966-07-11 | 1967-06-27 | Verfahren zur Herstellung neuer cyclischer Phosphorsäure- und Thiophosphorsäurederivate |
| SE09970/67*A SE330174B (fi) | 1966-07-11 | 1967-06-30 | |
| BE700711D BE700711A (fi) | 1966-07-11 | 1967-06-30 | |
| ES342646A ES342646A1 (es) | 1966-07-11 | 1967-07-05 | Procedimiento para la fabricacion de nuevas amidas y este- ramidas n-sustituidas de acido fosforico y tiofosforico. |
| IL28263A IL28263A (en) | 1966-07-11 | 1967-07-05 | Cyclic phosphoric acid derivatives and their production |
| FI671879A FI48602C (fi) | 1966-07-11 | 1967-07-06 | Menetelmä terapeuttisesti vaikuttavien syklisten fosforihappojohdannai sten valmistamiseksi. |
| CH967367A CH510699A (de) | 1966-07-11 | 1967-07-07 | Verfahren zur Herstellung von neuen Phosphorsäure- und Thiophosphorsäurederivaten |
| CH1880170A CH509353A (de) | 1966-07-11 | 1967-07-07 | Verfahren zur Herstellung von neuen Phosphorsäure- und Thiophosphorsäurederivaten |
| OA53002A OA02679A (fr) | 1966-07-11 | 1967-07-07 | Procédé de préparations d'amides et d'amides d'esters N. substitués nouveaux d'acide phosphorique ou thiophosphorique. |
| CH1880070A CH512520A (de) | 1966-07-11 | 1967-07-07 | Verfahren zur Herstellung von neuen Phosphorsäure- und Thiophosphorsäurederivaten |
| JP42044086A JPS5247477B1 (fi) | 1966-07-11 | 1967-07-10 | |
| DK353667AA DK119407B (da) | 1966-07-11 | 1967-07-10 | Analogifremgangsmaade til fremstilling af cykliske fosforsyrederivater |
| SU1172379A SU289596A1 (ru) | 1967-07-11 | СПОСОБ ПОЛУЧЕНИЯ ЦИКЛИЧЕСКИХ ДИАМИДОЭФИРОВФОСФОРНОЙ кислоты | |
| NL676709606A NL148323B (nl) | 1966-07-11 | 1967-07-11 | Werkwijze voor het bereiden van cytostatisch actieve fosforzuuresteramiden en daaruit verkregen gevormde geneesmiddelen. |
| FR113841A FR6695M (fi) | 1966-07-11 | 1967-07-11 | |
| GB31849/67A GB1188159A (en) | 1966-07-11 | 1967-07-11 | Process for the production of New N-Substituted Amides and Esteramides of Phosphoric and Thiophosphoric Acid |
| US00106569A US3732340A (en) | 1966-07-11 | 1971-01-14 | N',o-propylene phosphoric acid ester diamides |
| YU03284/72A YU36187B (en) | 1966-07-11 | 1972-12-28 | Process for obtaining novel cyclic phosphoric acid derivatives |
| YU2251/74A YU39527B (en) | 1966-07-11 | 1974-08-16 | Process for the manufacture of new cyclic derivatives of phosphoric acid |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1966A0052989 DE1645921C3 (de) | 1966-07-11 | 1966-07-11 | 2-Oxo-13,2-osazaphosphorinane, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate |
| US10656971A | 1971-01-14 | 1971-01-14 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE1645921A1 DE1645921A1 (de) | 1970-07-16 |
| DE1645921B2 DE1645921B2 (de) | 1978-02-09 |
| DE1645921C3 true DE1645921C3 (de) | 1978-10-12 |
Family
ID=25964360
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE1966A0052989 Expired DE1645921C3 (de) | 1966-07-11 | 1966-07-11 | 2-Oxo-13,2-osazaphosphorinane, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate |
Country Status (12)
| Country | Link |
|---|---|
| BE (1) | BE700711A (fi) |
| CH (1) | CH510699A (fi) |
| DE (1) | DE1645921C3 (fi) |
| DK (1) | DK119407B (fi) |
| ES (1) | ES342646A1 (fi) |
| FI (1) | FI48602C (fi) |
| FR (1) | FR6695M (fi) |
| GB (1) | GB1188159A (fi) |
| LU (1) | LU53924A1 (fi) |
| NL (1) | NL148323B (fi) |
| SE (1) | SE330174B (fi) |
| YU (2) | YU36187B (fi) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3220672A1 (de) * | 1981-03-24 | 1983-12-08 | Asta-Werke Ag, Chemische Fabrik, 4800 Bielefeld | Cis-oxazaphosphorin-4-thio-alkansulfonsaeuren, ihre neutralen salze, verfahren zur herstellung derselben und diese enthaltenden pharmazeutischen praeparate |
| DE3111428A1 (de) * | 1981-03-24 | 1982-10-07 | Asta-Werke Ag, Chemische Fabrik, 4800 Bielefeld | Oxazaphosphorin-4-thio-alkansulfonsaeuren und deren neutrale salze, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische zubereitungen |
| DE3220432A1 (de) * | 1981-03-24 | 1983-12-01 | Asta-Werke Ag, Chemische Fabrik, 4800 Bielefeld | Oxazaphosphorin-4-thio-alkansulfonsaeure, ihre neutralen salze, verfahren zur herstellung derselben und diese enthaltenden pharmazeutischen praeparate |
| DE3133077A1 (de) * | 1981-08-21 | 1983-03-10 | Henkel KGaA, 4000 Düsseldorf | Neue cytostatisch wirksame epoxidgruppen tragende 1,3,2-oxazaphosphorin-verbindungen, verfahren zu ihrer herstellung sowie ihre verwendung in pharmazeutischen zubereitungen |
| EP0235661A3 (de) * | 1986-02-22 | 1989-01-11 | ASTA Pharma Aktiengesellschaft | Neue heterocyclische Verbindungen mit einem 2-[2-(N,N-Bis-(2-chlorethyl)-diamido-phosphoryl-oxy)ethyl]-Rest |
| DE3862595D1 (de) * | 1987-03-06 | 1991-06-06 | Asta Pharma Ag | Verfahren zur herstellung von ifosfamid mit verbesserten eigenschaften. |
| GB9323399D0 (en) * | 1993-11-12 | 1994-01-05 | Univ Newcastle Ventures Ltd | Pharmaceutical formulations |
| DE19739159C1 (de) * | 1997-09-06 | 1999-01-28 | Asta Medica Ag | Verfahren zur Herstellung von Oxazaphosphorin-2-aminen |
-
1966
- 1966-07-11 DE DE1966A0052989 patent/DE1645921C3/de not_active Expired
-
1967
- 1967-06-20 LU LU53924D patent/LU53924A1/xx unknown
- 1967-06-30 BE BE700711D patent/BE700711A/xx not_active IP Right Cessation
- 1967-06-30 SE SE09970/67*A patent/SE330174B/xx unknown
- 1967-07-05 ES ES342646A patent/ES342646A1/es not_active Expired
- 1967-07-06 FI FI671879A patent/FI48602C/fi active
- 1967-07-07 CH CH967367A patent/CH510699A/de not_active IP Right Cessation
- 1967-07-10 DK DK353667AA patent/DK119407B/da not_active IP Right Cessation
- 1967-07-11 GB GB31849/67A patent/GB1188159A/en not_active Expired
- 1967-07-11 NL NL676709606A patent/NL148323B/xx not_active IP Right Cessation
- 1967-07-11 FR FR113841A patent/FR6695M/fr not_active Expired
-
1972
- 1972-12-28 YU YU03284/72A patent/YU36187B/xx unknown
-
1974
- 1974-08-16 YU YU2251/74A patent/YU39527B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| YU36187B (en) | 1982-02-25 |
| YU225174A (en) | 1982-02-28 |
| SE330174B (fi) | 1970-11-09 |
| BE700711A (fi) | 1967-12-01 |
| FI48602B (fi) | 1974-07-31 |
| GB1188159A (en) | 1970-04-15 |
| YU39527B (en) | 1984-12-31 |
| FR6695M (fi) | 1969-02-10 |
| LU53924A1 (fi) | 1967-08-21 |
| FI48602C (fi) | 1974-11-11 |
| NL148323B (nl) | 1976-01-15 |
| NL6709606A (fi) | 1968-01-12 |
| CH510699A (de) | 1971-07-31 |
| DE1645921B2 (de) | 1978-02-09 |
| DE1645921A1 (de) | 1970-07-16 |
| YU328472A (en) | 1981-06-30 |
| ES342646A1 (es) | 1968-10-16 |
| DK119407B (da) | 1970-12-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C3 | Grant after two publication steps (3rd publication) |