CN112513056A - 三甲铵基乙硫磷酰二乙酯碘化物的制备方法 - Google Patents
三甲铵基乙硫磷酰二乙酯碘化物的制备方法 Download PDFInfo
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- CN112513056A CN112513056A CN201980049986.2A CN201980049986A CN112513056A CN 112513056 A CN112513056 A CN 112513056A CN 201980049986 A CN201980049986 A CN 201980049986A CN 112513056 A CN112513056 A CN 112513056A
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- Prior art keywords
- diethyl
- dimethylamino
- reacting
- iodide
- reaction
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- -1 ethyl phosphono Chemical group 0.000 title claims abstract description 61
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 title claims abstract description 13
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 title abstract description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 172
- 238000000034 method Methods 0.000 claims abstract description 42
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 26
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims abstract description 23
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims abstract description 7
- RIZMRRKBZQXFOY-UHFFFAOYSA-N ethion Chemical compound CCOP(=S)(OCC)SCSP(=S)(OCC)OCC RIZMRRKBZQXFOY-UHFFFAOYSA-N 0.000 claims abstract description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 88
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 86
- 238000006243 chemical reaction Methods 0.000 claims description 79
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 66
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 57
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 54
- 239000002904 solvent Substances 0.000 claims description 51
- 239000003960 organic solvent Substances 0.000 claims description 49
- WQMAANNAZKNUDL-UHFFFAOYSA-N 2-dimethylaminoethyl chloride Chemical compound CN(C)CCCl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 claims description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 42
- 230000015572 biosynthetic process Effects 0.000 claims description 42
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 35
- 238000001953 recrystallisation Methods 0.000 claims description 33
- 239000011734 sodium Substances 0.000 claims description 32
- 229910052708 sodium Inorganic materials 0.000 claims description 31
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 30
- 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 claims description 27
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 27
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 24
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 claims description 23
- QNWKSLSPYNPZFE-UHFFFAOYSA-N 2-[bis(methylamino)amino]ethanol Chemical compound CNN(NC)CCO QNWKSLSPYNPZFE-UHFFFAOYSA-N 0.000 claims description 15
- XFTHQVHWPHUOFT-UHFFFAOYSA-N 2-diethoxyphosphinothioyloxy-n,n-dimethylethanamine Chemical compound CCOP(=S)(OCC)OCCN(C)C XFTHQVHWPHUOFT-UHFFFAOYSA-N 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 13
- 229910052751 metal Inorganic materials 0.000 claims description 13
- 239000002184 metal Substances 0.000 claims description 13
- PKUWKAXTAVNIJR-UHFFFAOYSA-N O,O-diethyl hydrogen thiophosphate Chemical compound CCOP(O)(=S)OCC PKUWKAXTAVNIJR-UHFFFAOYSA-N 0.000 claims description 10
- 239000003208 petroleum Substances 0.000 claims description 7
- 159000000000 sodium salts Chemical class 0.000 claims description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 229910019142 PO4 Inorganic materials 0.000 claims description 5
- 239000010452 phosphate Substances 0.000 claims description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 3
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 claims 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 claims 2
- 150000008282 halocarbons Chemical class 0.000 claims 2
- 229940102396 methyl bromide Drugs 0.000 claims 1
- 229940050176 methyl chloride Drugs 0.000 claims 1
- MNTLJDNIQGVGEC-UHFFFAOYSA-N n,n-dimethylmethanamine;trihydroxy(sulfanylidene)-$l^{5}-phosphane Chemical compound CN(C)C.CN(C)C.CN(C)C.OP(O)(O)=S MNTLJDNIQGVGEC-UHFFFAOYSA-N 0.000 claims 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 description 37
- 238000001914 filtration Methods 0.000 description 26
- 239000000243 solution Substances 0.000 description 26
- 238000001035 drying Methods 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000000543 intermediate Substances 0.000 description 19
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- 238000005406 washing Methods 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 239000007787 solid Substances 0.000 description 14
- 239000012043 crude product Substances 0.000 description 13
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- 239000012046 mixed solvent Substances 0.000 description 12
- 239000000047 product Substances 0.000 description 11
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 238000004821 distillation Methods 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 239000012065 filter cake Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 231100000331 toxic Toxicity 0.000 description 6
- 230000002588 toxic effect Effects 0.000 description 6
- PURYCGFBBYVQEQ-UHFFFAOYSA-N 1-(dimethylamino)ethanethiol Chemical compound CC(S)N(C)C PURYCGFBBYVQEQ-UHFFFAOYSA-N 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 238000011033 desalting Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000004108 freeze drying Methods 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- DTKIFYHPOFQANW-UHFFFAOYSA-N 2-(2,2-dimethylhydrazinyl)ethanol Chemical compound CN(C)NCCO DTKIFYHPOFQANW-UHFFFAOYSA-N 0.000 description 4
- 208000010412 Glaucoma Diseases 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 238000009987 spinning Methods 0.000 description 4
- 150000003462 sulfoxides Chemical class 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000003889 eye drop Substances 0.000 description 3
- 229940012356 eye drops Drugs 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- DENMGZODXQRYAR-UHFFFAOYSA-N 2-(dimethylamino)ethanethiol Chemical compound CN(C)CCS DENMGZODXQRYAR-UHFFFAOYSA-N 0.000 description 2
- LVCHXPHUKPLVRQ-UHFFFAOYSA-N 2-bromo-n,n-dimethylethanamine Chemical compound CN(C)CCBr LVCHXPHUKPLVRQ-UHFFFAOYSA-N 0.000 description 2
- MFRUVSDIZTZFFL-UHFFFAOYSA-N 2-bromo-n,n-dimethylethanamine;hydrobromide Chemical compound [Br-].C[NH+](C)CCBr MFRUVSDIZTZFFL-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 229940122041 Cholinesterase inhibitor Drugs 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- PKUWKAXTAVNIJR-UHFFFAOYSA-M O,O-diethyl thiophosphate Chemical compound CCOP([O-])(=S)OCC PKUWKAXTAVNIJR-UHFFFAOYSA-M 0.000 description 2
- OBHAEIFSQNNSFV-UHFFFAOYSA-N P(OCC)(OCC)([O-])=S.[I-].C[NH+](C)C.C[NH+](C)C Chemical compound P(OCC)(OCC)([O-])=S.[I-].C[NH+](C)C.C[NH+](C)C OBHAEIFSQNNSFV-UHFFFAOYSA-N 0.000 description 2
- 208000004350 Strabismus Diseases 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 230000000711 cancerogenic effect Effects 0.000 description 2
- 231100000315 carcinogenic Toxicity 0.000 description 2
- 239000003183 carcinogenic agent Substances 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 239000000544 cholinesterase inhibitor Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 2
- OVXQHPWHMXOFRD-UHFFFAOYSA-M ecothiopate iodide Chemical compound [I-].CCOP(=O)(OCC)SCC[N+](C)(C)C OVXQHPWHMXOFRD-UHFFFAOYSA-M 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005580 one pot reaction Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- BYMVZHORNHZYPQ-UHFFFAOYSA-N sodium;diethyl phosphite Chemical compound [Na+].CCOP([O-])OCC BYMVZHORNHZYPQ-UHFFFAOYSA-N 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 230000017105 transposition Effects 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- JRPNCILONFCLQX-UHFFFAOYSA-N 1,2-dichloro-n,n-dimethylethanamine Chemical compound CN(C)C(Cl)CCl JRPNCILONFCLQX-UHFFFAOYSA-N 0.000 description 1
- NTHKNMPHBNQTJM-UHFFFAOYSA-N 1-chloro-n,n-dimethylethanamine;hydrochloride Chemical compound Cl.CC(Cl)N(C)C NTHKNMPHBNQTJM-UHFFFAOYSA-N 0.000 description 1
- CQJDAFVWXFTRJN-UHFFFAOYSA-N 2-iodo-n,n-dimethylethanamine Chemical compound CN(C)CCI CQJDAFVWXFTRJN-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 208000001692 Esotropia Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010022945 Iris adhesions Diseases 0.000 description 1
- 201000003533 Leber congenital amaurosis Diseases 0.000 description 1
- 208000035725 Macular cyst Diseases 0.000 description 1
- 206010030043 Ocular hypertension Diseases 0.000 description 1
- 206010030348 Open-Angle Glaucoma Diseases 0.000 description 1
- 208000002367 Retinal Perforations Diseases 0.000 description 1
- 208000032458 Retinopathy solar Diseases 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 210000002159 anterior chamber Anatomy 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- KMJJJTCKNZYTEY-UHFFFAOYSA-N chloro-diethoxy-sulfanylidene-$l^{5}-phosphane Chemical compound CCOP(Cl)(=S)OCC KMJJJTCKNZYTEY-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229910001867 inorganic solvent Inorganic materials 0.000 description 1
- 239000003049 inorganic solvent Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 208000029233 macular holes Diseases 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 208000001491 myopia Diseases 0.000 description 1
- 230000004379 myopia Effects 0.000 description 1
- LKDYWVBMAOFKFE-UHFFFAOYSA-N n,n-dimethylethanamine;dihydrochloride Chemical compound Cl.[Cl-].CC[NH+](C)C LKDYWVBMAOFKFE-UHFFFAOYSA-N 0.000 description 1
- KSKTVNNRMXUMIY-UHFFFAOYSA-N n,n-dimethylethanamine;hydrochloride Chemical compound Cl.CCN(C)C KSKTVNNRMXUMIY-UHFFFAOYSA-N 0.000 description 1
- DAZXVJBJRMWXJP-UHFFFAOYSA-N n,n-dimethylethylamine Chemical compound CCN(C)C DAZXVJBJRMWXJP-UHFFFAOYSA-N 0.000 description 1
- MAGVJLLHDZWQFM-UHFFFAOYSA-N n-chloro-n-methylmethanamine Chemical compound CN(C)Cl MAGVJLLHDZWQFM-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 125000001863 phosphorothioyl group Chemical group *P(*)(*)=S 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 201000010041 presbyopia Diseases 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000010344 pupil dilation Effects 0.000 description 1
- 208000004644 retinal vein occlusion Diseases 0.000 description 1
- WFKJEZKHPGDCRK-UHFFFAOYSA-M sodium;2,2,2-trichloroethyl hydrogen phosphate Chemical compound [Na+].OP([O-])(=O)OCC(Cl)(Cl)Cl WFKJEZKHPGDCRK-UHFFFAOYSA-M 0.000 description 1
- YMPPRYJBYFNJTO-UHFFFAOYSA-M sodium;diethoxy-oxido-sulfanylidene-$l^{5}-phosphane Chemical compound [Na+].CCOP([O-])(=S)OCC YMPPRYJBYFNJTO-UHFFFAOYSA-M 0.000 description 1
- 201000000824 solar retinopathy Diseases 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing 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
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/16—Esters of thiophosphoric acids or thiophosphorous acids
- C07F9/165—Esters of thiophosphoric acids
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)
Abstract
本文涉及三甲铵基乙硫磷酰二乙酯碘化物的制备方法,包括：将O,O‑二乙基硫代磷酸钠盐与2‑二甲氨基卤乙烷反应得到二甲氨基乙硫磷酰二乙酯；将二甲氨基乙硫磷酰二乙酯与碘甲烷反应得到三甲铵基乙硫磷酰二乙酯碘化物。此处提供的制备三甲铵基乙硫磷酰二乙酯碘化物的方法简单易行、成本低、收率高、适合大规模工业化生产。
Description
PCT国内申请，说明书已公开。
Claims (11)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810843258 | 2018-07-27 | ||
| CN2018108432586 | 2018-07-27 | ||
| PCT/CN2019/098001 WO2020020370A1 (zh) | 2018-07-27 | 2019-07-26 | 三甲铵基乙硫磷酰二乙酯碘化物的制备方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112513056A true CN112513056A (zh) | 2021-03-16 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201980049986.2A Pending CN112513056A (zh) | 2018-07-27 | 2019-07-26 | 三甲铵基乙硫磷酰二乙酯碘化物的制备方法 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN112513056A (zh) |
| WO (1) | WO2020020370A1 (zh) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB738839A (en) * | 1952-11-19 | 1955-10-19 | Ici Ltd | New basic esters of phosphorus-containing acids |
| GB814264A (en) * | 1956-09-17 | 1959-06-03 | Ici Ltd | New pesticidal basic esters of phosphorus-containing acids |
| US2943015A (en) * | 1956-10-19 | 1960-06-28 | Ici Ltd | Omicron:omicron'-diethyl s-(beta-dimethyl amino-beta-methyl)-propyl phosphorothiolates and pesticidal compositions containing same |
| CN103408432A (zh) * | 2013-07-01 | 2013-11-27 | 昆山三友医药原料有限公司 | 2-二甲氨基氯乙烷盐酸盐的合成工艺 |
| WO2015114470A1 (en) * | 2014-01-31 | 2015-08-06 | Shilpa Medicare Limited | Echothiophate iodide process |
| CN105524104A (zh) * | 2015-12-03 | 2016-04-27 | 清华大学 | 硫代磷酸酯衍生物与过量溴乙酮基芳环物的反应及产物 |
-
2019
- 2019-07-26 WO PCT/CN2019/098001 patent/WO2020020370A1/zh active Application Filing
- 2019-07-26 CN CN201980049986.2A patent/CN112513056A/zh active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB738839A (en) * | 1952-11-19 | 1955-10-19 | Ici Ltd | New basic esters of phosphorus-containing acids |
| GB814264A (en) * | 1956-09-17 | 1959-06-03 | Ici Ltd | New pesticidal basic esters of phosphorus-containing acids |
| US2943015A (en) * | 1956-10-19 | 1960-06-28 | Ici Ltd | Omicron:omicron'-diethyl s-(beta-dimethyl amino-beta-methyl)-propyl phosphorothiolates and pesticidal compositions containing same |
| CN103408432A (zh) * | 2013-07-01 | 2013-11-27 | 昆山三友医药原料有限公司 | 2-二甲氨基氯乙烷盐酸盐的合成工艺 |
| WO2015114470A1 (en) * | 2014-01-31 | 2015-08-06 | Shilpa Medicare Limited | Echothiophate iodide process |
| US20170002031A1 (en) * | 2014-01-31 | 2017-01-05 | Shilpa Medicare Limited | Echothiophate Iodide Process |
| CN105524104A (zh) * | 2015-12-03 | 2016-04-27 | 清华大学 | 硫代磷酸酯衍生物与过量溴乙酮基芳环物的反应及产物 |
Non-Patent Citations (4)
| Title |
|---|
| FOREST J. ROBERTSON，等: "Phosphorothioic Acids and Related Compounds as Surrogates for H2S—Synthesis of Chiral Tetrahydrothiophenes", 《J. AM. CHEM. SOC.》 * |
| GAVRIEL A，等: "Synthesis and properties of 2-S-(N,N-dialkylamino)ethyl)thio-1,3,2-dioxaphosphorinane 2-oxide and of the corresponding quaternary derivatives as potential nontoxic antiglaucoma agents", 《J MED CHEM》 * |
| 夏彩云，等: "国外主要农药品种的合成路线(三)", 《农药》 * |
| 郭宗儒，等: "碘磷灵的合成", 《医药工业》 * |
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| WO2020020370A1 (zh) | 2020-01-30 |
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