IL134507A - Method for preparing oxazaphosphorin-2-amines - Google Patents
Method for preparing oxazaphosphorin-2-aminesInfo
- Publication number
- IL134507A IL134507A IL13450798A IL13450798A IL134507A IL 134507 A IL134507 A IL 134507A IL 13450798 A IL13450798 A IL 13450798A IL 13450798 A IL13450798 A IL 13450798A IL 134507 A IL134507 A IL 134507A
- Authority
- IL
- Israel
- Prior art keywords
- formula
- compound
- chloroethyl
- employed
- amine
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 28
- VFSGCCSSYZKOSH-UHFFFAOYSA-N oxazaphosphinin-2-amine Chemical class NN1OC=CC=P1 VFSGCCSSYZKOSH-UHFFFAOYSA-N 0.000 title claims abstract description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 87
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 65
- 150000001875 compounds Chemical class 0.000 claims abstract description 50
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims abstract description 35
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000002585 base Substances 0.000 claims abstract description 27
- 150000001412 amines Chemical class 0.000 claims abstract description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000000203 mixture Substances 0.000 claims abstract description 16
- -1 2-mesyloxyethyl Chemical group 0.000 claims abstract description 15
- 125000005999 2-bromoethyl group Chemical group 0.000 claims abstract description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims abstract description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000004069 aziridinyl group Chemical group 0.000 claims abstract description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052794 bromium Chemical group 0.000 claims abstract description 6
- 238000002955 isolation Methods 0.000 claims abstract description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 5
- 230000000694 effects Effects 0.000 claims abstract description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims abstract description 4
- 150000001298 alcohols Chemical class 0.000 claims abstract description 4
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims abstract description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000011230 binding agent Substances 0.000 claims abstract description 3
- 239000000460 chlorine Substances 0.000 claims abstract description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims abstract description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000001931 aliphatic group Chemical group 0.000 claims abstract 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims abstract 2
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract 2
- 150000001340 alkali metals Chemical class 0.000 claims abstract 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims abstract 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims abstract 2
- 150000004292 cyclic ethers Chemical class 0.000 claims abstract 2
- 229930195733 hydrocarbon Natural products 0.000 claims abstract 2
- 150000002430 hydrocarbons Chemical class 0.000 claims abstract 2
- 239000003701 inert diluent Substances 0.000 claims abstract 2
- 239000012442 inert solvent Substances 0.000 claims abstract 2
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 7
- 239000007858 starting material Substances 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 4
- 235000011152 sodium sulphate Nutrition 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 239000001110 calcium chloride Substances 0.000 claims description 3
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- ZGGGBVXKANMEPP-UHFFFAOYSA-N 3-chloro-n-(2-chloroethyl)propan-1-amine;hydron;chloride Chemical compound Cl.ClCCCNCCCl ZGGGBVXKANMEPP-UHFFFAOYSA-N 0.000 claims description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 2
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 claims description 2
- 239000002808 molecular sieve Substances 0.000 claims description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 239000002253 acid Substances 0.000 abstract description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 50
- 229940086542 triethylamine Drugs 0.000 description 27
- 238000003756 stirring Methods 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 13
- UBRSKPGONDTDNE-UHFFFAOYSA-N 3-(2-chloroethylamino)propan-1-ol;hydrochloride Chemical compound Cl.OCCCNCCCl UBRSKPGONDTDNE-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 11
- 238000002844 melting Methods 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- ZSZKJARKHWCBJK-UHFFFAOYSA-N 2-[[3-(2-chloroethyl)-2-oxo-1,3,2$l^{5}-oxazaphosphinan-2-yl]amino]ethyl methanesulfonate Chemical compound CS(=O)(=O)OCCNP1(=O)OCCCN1CCCl ZSZKJARKHWCBJK-UHFFFAOYSA-N 0.000 description 9
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 9
- 229960001101 ifosfamide Drugs 0.000 description 9
- 229950008275 sufosfamide Drugs 0.000 description 9
- 238000007792 addition Methods 0.000 description 8
- VKPPFDPXZWFDFA-UHFFFAOYSA-N 2-chloroethanamine Chemical compound NCCCl VKPPFDPXZWFDFA-UHFFFAOYSA-N 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- UMKFEPPTGMDVMI-UHFFFAOYSA-N trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 0.000 description 6
- 238000004679 31P NMR spectroscopy Methods 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- NLWKFGLMXIKYHZ-UHFFFAOYSA-N NP(N)(=O)N(Cl)Cl Chemical compound NP(N)(=O)N(Cl)Cl NLWKFGLMXIKYHZ-UHFFFAOYSA-N 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- 101150041968 CDC13 gene Proteins 0.000 description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- PWOQRKCAHTVFLB-UHFFFAOYSA-N cyclophosphamide hydrate Chemical compound O.ClCCN(CCCl)P1(=O)NCCCO1 PWOQRKCAHTVFLB-UHFFFAOYSA-N 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 239000011574 phosphorus Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 229960000875 trofosfamide Drugs 0.000 description 4
- HOMGKSMUEGBAAB-CQSZACIVSA-N (2r)-n,3-bis(2-chloroethyl)-2-oxo-1,3,2$l^{5}-oxazaphosphinan-2-amine Chemical compound ClCCN[P@@]1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-CQSZACIVSA-N 0.000 description 3
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 239000000824 cytostatic agent Substances 0.000 description 3
- 230000001085 cytostatic effect Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000005580 one pot reaction Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000007086 side reaction Methods 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 230000001861 immunosuppressant effect Effects 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 238000003328 mesylation reaction Methods 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 150000003460 sulfonic acids Chemical class 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- YMDZDFSUDFLGMX-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)ethanamine;hydron;chloride Chemical compound [Cl-].ClCC[NH2+]CCCl YMDZDFSUDFLGMX-UHFFFAOYSA-N 0.000 description 1
- RUJHATQMIMUYKD-UHFFFAOYSA-N 2-naphthalen-1-ylethanamine Chemical compound C1=CC=C2C(CCN)=CC=CC2=C1 RUJHATQMIMUYKD-UHFFFAOYSA-N 0.000 description 1
- ZZVDXRCAGGQFAK-UHFFFAOYSA-N 2h-oxazaphosphinine Chemical class N1OC=CC=P1 ZZVDXRCAGGQFAK-UHFFFAOYSA-N 0.000 description 1
- MGDSRXCBGQRITM-UHFFFAOYSA-N 3-(aziridin-1-yl)propan-1-ol Chemical compound OCCCN1CC1 MGDSRXCBGQRITM-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002894 chemical waste Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 125000004119 disulfanediyl group Chemical class *SS* 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 238000001394 phosphorus-31 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Transplantation (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19739159A DE19739159C1 (de) | 1997-09-06 | 1997-09-06 | Verfahren zur Herstellung von Oxazaphosphorin-2-aminen |
| PCT/EP1998/005170 WO1999012942A1 (fr) | 1997-09-06 | 1998-08-14 | Procede pour la preparation d'oxazaphosphorin-2-amines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL134507A0 IL134507A0 (en) | 2001-04-30 |
| IL134507A true IL134507A (en) | 2004-06-20 |
Family
ID=7841505
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL13450798A IL134507A (en) | 1997-09-06 | 1998-08-14 | Method for preparing oxazaphosphorin-2-amines |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US6187941B1 (fr) |
| EP (1) | EP1012152B1 (fr) |
| JP (1) | JP4278859B2 (fr) |
| CN (1) | CN1147498C (fr) |
| AR (1) | AR013467A1 (fr) |
| AT (1) | ATE225797T1 (fr) |
| BR (1) | BR9814266B1 (fr) |
| CA (1) | CA2301104C (fr) |
| DE (2) | DE19739159C1 (fr) |
| DK (1) | DK1012152T3 (fr) |
| ES (1) | ES2185220T3 (fr) |
| HK (1) | HK1030422A1 (fr) |
| HU (1) | HU226887B1 (fr) |
| IL (1) | IL134507A (fr) |
| IN (1) | IN186170B (fr) |
| PL (1) | PL190097B1 (fr) |
| PT (1) | PT1012152E (fr) |
| WO (1) | WO1999012942A1 (fr) |
| ZA (1) | ZA987741B (fr) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1607204B (zh) * | 2003-10-13 | 2011-10-26 | 北京大学 | 环磷酰胺季铵盐衍生物及其合成和应用 |
| US20110054081A1 (en) * | 2009-09-02 | 2011-03-03 | Frank Dierschke | Formulation and its use |
| FR2968662B1 (fr) * | 2010-12-10 | 2013-11-22 | Roussy Inst Gustave | Nouveaux derives d'oxazaphosphorines pre-activees, utilisation et methode de preparation |
| WO2016156927A1 (fr) | 2015-04-02 | 2016-10-06 | PRZEDSIĘBIORSTWO PRODUKCYJNO-WDROŻENIOWE IFOTAM Sp. z o.o. | Procédé de production de n,n-bis (2-chloroéthyl)tétrahydro-2 h-1,3,2-oxazaphosphorine-2-amine 2-oxyde |
| CN107936061B (zh) * | 2017-12-28 | 2019-08-06 | 山东铂源药业有限公司 | 一种环磷酰胺的合成方法 |
| CN109535201B (zh) * | 2019-01-25 | 2020-04-03 | 连云港贵科药业有限公司 | 一种环磷酰胺的合成方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL222157A (fr) * | 1956-12-20 | |||
| US3732340A (en) * | 1966-07-11 | 1973-05-08 | Asta Werke Ag Chem Fab | N',o-propylene phosphoric acid ester diamides |
| DE1645921C3 (de) * | 1966-07-11 | 1978-10-12 | Asta-Werke Ag Chemische Fabrik, 4800 Bielefeld | 2-Oxo-13,2-osazaphosphorinane, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate |
| GB1235022A (en) * | 1969-06-04 | 1971-06-09 | Laeaeke Ag | A new method for the production of cyclophosphamide |
| JPS54157580A (en) * | 1978-05-29 | 1979-12-12 | Otsuka Pharmaceut Co Ltd | Optically active oxazaphosphorine derivative |
| JPS54157581A (en) * | 1978-05-29 | 1979-12-12 | Otsuka Pharmaceut Co Ltd | Oxazaphosphorine derivative |
| PL119971B1 (en) * | 1978-11-06 | 1982-02-27 | Polska Akad Nauk Centrum | Process for preparing optically active derivatives of 1,3,2-oxazaphosphorinane,2-oksazofosforinata |
| JPS5826919B2 (ja) * | 1978-11-07 | 1983-06-06 | 大塚製薬株式会社 | シクロ↓−１，３，２↓−オキサアザホスホル誘導体の製造法 |
| JPS5931787A (ja) * | 1982-08-13 | 1984-02-20 | Otsuka Pharmaceut Co Ltd | １，３，２−オキサアザホスホリナン−２−オキシド誘導体 |
| PL149593B1 (pl) * | 1986-12-18 | 1990-02-28 | Sposób wytwarzania n-acylowych pochodnych 1 , 3 , 2-oksazafosforinanu |
-
1997
- 1997-09-06 DE DE19739159A patent/DE19739159C1/de not_active Expired - Lifetime
-
1998
- 1998-08-14 EP EP98945245A patent/EP1012152B1/fr not_active Expired - Lifetime
- 1998-08-14 CA CA002301104A patent/CA2301104C/fr not_active Expired - Fee Related
- 1998-08-14 JP JP2000510748A patent/JP4278859B2/ja not_active Expired - Fee Related
- 1998-08-14 BR BRPI9814266-6A patent/BR9814266B1/pt not_active IP Right Cessation
- 1998-08-14 AT AT98945245T patent/ATE225797T1/de active
- 1998-08-14 WO PCT/EP1998/005170 patent/WO1999012942A1/fr active IP Right Grant
- 1998-08-14 ES ES98945245T patent/ES2185220T3/es not_active Expired - Lifetime
- 1998-08-14 DE DE59805920T patent/DE59805920D1/de not_active Expired - Lifetime
- 1998-08-14 IL IL13450798A patent/IL134507A/en not_active IP Right Cessation
- 1998-08-14 DK DK98945245T patent/DK1012152T3/da active
- 1998-08-14 PL PL98339188A patent/PL190097B1/pl unknown
- 1998-08-14 HU HU0003496A patent/HU226887B1/hu not_active IP Right Cessation
- 1998-08-14 CN CNB988087529A patent/CN1147498C/zh not_active Expired - Lifetime
- 1998-08-14 PT PT98945245T patent/PT1012152E/pt unknown
- 1998-08-26 ZA ZA987741A patent/ZA987741B/xx unknown
- 1998-09-01 IN IN1574CA1998 patent/IN186170B/en unknown
- 1998-09-04 AR ARP980104431A patent/AR013467A1/es active IP Right Grant
- 1998-09-08 US US09/149,099 patent/US6187941B1/en not_active Expired - Lifetime
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2001
- 2001-02-23 HK HK01101318A patent/HK1030422A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0003496A2 (hu) | 2002-11-28 |
| HU226887B1 (en) | 2010-01-28 |
| EP1012152B1 (fr) | 2002-10-09 |
| CA2301104A1 (fr) | 1999-03-18 |
| IN186170B (fr) | 2001-06-30 |
| DE59805920D1 (de) | 2002-11-14 |
| WO1999012942A1 (fr) | 1999-03-18 |
| DK1012152T3 (da) | 2003-02-10 |
| CN1147498C (zh) | 2004-04-28 |
| CA2301104C (fr) | 2009-10-20 |
| PL190097B1 (pl) | 2005-10-31 |
| ATE225797T1 (de) | 2002-10-15 |
| HK1030422A1 (en) | 2001-05-04 |
| US6187941B1 (en) | 2001-02-13 |
| JP4278859B2 (ja) | 2009-06-17 |
| HUP0003496A3 (en) | 2002-12-28 |
| BR9814266A (pt) | 2001-10-09 |
| EP1012152A1 (fr) | 2000-06-28 |
| ES2185220T3 (es) | 2003-04-16 |
| DE19739159C1 (de) | 1999-01-28 |
| IL134507A0 (en) | 2001-04-30 |
| ZA987741B (en) | 1998-10-08 |
| PL339188A1 (en) | 2000-12-04 |
| BR9814266B1 (pt) | 2009-05-05 |
| AR013467A1 (es) | 2000-12-27 |
| CN1268950A (zh) | 2000-10-04 |
| PT1012152E (pt) | 2003-02-28 |
| JP2001515910A (ja) | 2001-09-25 |
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