HU187685B - Process for preparing 2-oxo-1-/substituted phosphinyl/-azetidines - Google Patents
Process for preparing 2-oxo-1-/substituted phosphinyl/-azetidines Download PDFInfo
- Publication number
- HU187685B HU187685B HU82959A HU95982A HU187685B HU 187685 B HU187685 B HU 187685B HU 82959 A HU82959 A HU 82959A HU 95982 A HU95982 A HU 95982A HU 187685 B HU187685 B HU 187685B
- Authority
- HU
- Hungary
- Prior art keywords
- formula
- amino
- oxo
- alkyl
- azetidinyl
- Prior art date
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- 125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 title description 3
- 238000004519 manufacturing process Methods 0.000 title 1
- -1 2-oxo-1- (substituted phosphinyl) azetidines Chemical class 0.000 claims description 173
- 150000001875 compounds Chemical class 0.000 claims description 127
- 150000003839 salts Chemical class 0.000 claims description 35
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 claims description 34
- 238000000034 method Methods 0.000 claims description 31
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 27
- 150000002148 esters Chemical class 0.000 claims description 27
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 150000008064 anhydrides Chemical class 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 12
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 10
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 10
- 239000007858 starting material Substances 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 230000003213 activating effect Effects 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- 150000001768 cations Chemical class 0.000 claims description 3
- 150000003017 phosphorus Chemical class 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- 239000004480 active ingredient Substances 0.000 claims 2
- 229910001413 alkali metal ion Inorganic materials 0.000 claims 2
- 150000004820 halides Chemical class 0.000 claims 2
- 150000008065 acid anhydrides Chemical class 0.000 claims 1
- 125000004423 acyloxy group Chemical group 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 239000012059 conventional drug carrier Substances 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000000945 filler Substances 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical class [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 150000003952 β-lactams Chemical class 0.000 abstract description 13
- 125000001424 substituent group Chemical group 0.000 abstract description 6
- 230000000844 anti-bacterial effect Effects 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 183
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 168
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 154
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 153
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 138
- 239000000203 mixture Substances 0.000 description 116
- 239000000243 solution Substances 0.000 description 98
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 93
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 60
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 56
- 239000011541 reaction mixture Substances 0.000 description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
- 239000002904 solvent Substances 0.000 description 51
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 49
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 47
- 239000000047 product Substances 0.000 description 43
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
- 239000007787 solid Substances 0.000 description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 35
- 239000003921 oil Substances 0.000 description 35
- 238000003756 stirring Methods 0.000 description 32
- 238000004458 analytical method Methods 0.000 description 31
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 30
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- 239000003039 volatile agent Substances 0.000 description 28
- 239000011347 resin Substances 0.000 description 27
- 229920005989 resin Polymers 0.000 description 27
- 239000000843 powder Substances 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 238000010828 elution Methods 0.000 description 20
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
- 229910052757 nitrogen Inorganic materials 0.000 description 19
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 19
- 238000004587 chromatography analysis Methods 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 17
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 17
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 17
- 229910052938 sodium sulfate Inorganic materials 0.000 description 17
- 235000011152 sodium sulphate Nutrition 0.000 description 17
- 229940086542 triethylamine Drugs 0.000 description 17
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 16
- 235000015497 potassium bicarbonate Nutrition 0.000 description 16
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 16
- 239000011736 potassium bicarbonate Substances 0.000 description 16
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 15
- 238000001816 cooling Methods 0.000 description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 15
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 15
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 14
- 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 description 14
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 14
- 229910052700 potassium Inorganic materials 0.000 description 14
- 239000011591 potassium Substances 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 239000003456 ion exchange resin Substances 0.000 description 12
- 229920003303 ion-exchange polymer Polymers 0.000 description 12
- NLARCUDOUOQRPB-WTKPLQERSA-N (2z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetic acid Chemical compound CO\N=C(/C(O)=O)C1=CSC(N)=N1 NLARCUDOUOQRPB-WTKPLQERSA-N 0.000 description 11
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 11
- 239000003208 petroleum Substances 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 238000004108 freeze drying Methods 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 125000004442 acylamino group Chemical group 0.000 description 9
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 9
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical class [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 238000001665 trituration Methods 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- 239000008363 phosphate buffer Substances 0.000 description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 7
- NQXRQYKIEKLAHI-VIFPVBQESA-N benzyl n-[(3s)-2-oxoazetidin-3-yl]carbamate Chemical compound C=1C=CC=CC=1COC(=O)N[C@H]1CNC1=O NQXRQYKIEKLAHI-VIFPVBQESA-N 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- SIOVKLKJSOKLIF-UHFFFAOYSA-N bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)OC(C)=N[Si](C)(C)C SIOVKLKJSOKLIF-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- BCIYLYBVFPCPST-UQQQWYQISA-N (2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(1-benzhydryloxy-2-methyl-1-oxopropan-2-yl)oxyiminoacetic acid Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)OC(=O)C(C)(C)O\N=C(/C(O)=O)C1=CSC(N)=N1 BCIYLYBVFPCPST-UQQQWYQISA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 5
- 238000005917 acylation reaction Methods 0.000 description 5
- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 150000007530 organic bases Chemical class 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 5
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 4
- NGFFLHMFSINFGB-UHFFFAOYSA-N [chloro(methoxy)phosphoryl]oxymethane Chemical compound COP(Cl)(=O)OC NGFFLHMFSINFGB-UHFFFAOYSA-N 0.000 description 4
- 230000010933 acylation Effects 0.000 description 4
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 description 4
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 230000026731 phosphorylation Effects 0.000 description 4
- 238000006366 phosphorylation reaction Methods 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000002516 radical scavenger Substances 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- 239000002132 β-lactam antibiotic Substances 0.000 description 4
- 229940124586 β-lactam antibiotics Drugs 0.000 description 4
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 3
- NVEQKTJCRXBWHS-UHFFFAOYSA-N 3-azidoazetidin-2-one Chemical compound [N-]=[N+]=NC1CNC1=O NVEQKTJCRXBWHS-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000003729 cation exchange resin Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 150000002960 penicillins Chemical class 0.000 description 3
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- TWTDGXUOYAMFLW-UHFFFAOYSA-N 1-dichlorophosphoryloxy-2-fluoroethane Chemical compound FCCOP(Cl)(Cl)=O TWTDGXUOYAMFLW-UHFFFAOYSA-N 0.000 description 2
- RNXHHJQBVBRJMB-UHFFFAOYSA-N 1-dichlorophosphoryloxybutane Chemical compound CCCCOP(Cl)(Cl)=O RNXHHJQBVBRJMB-UHFFFAOYSA-N 0.000 description 2
- WSGFGKYOQQUFQV-UHFFFAOYSA-N 3-hydroxy-2H-1,3-benzothiazole hydrate Chemical compound C1N(C2=CC=CC=C2S1)O.O WSGFGKYOQQUFQV-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
- 229930186147 Cephalosporin Natural products 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
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- 235000011164 potassium chloride Nutrition 0.000 description 1
- WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- CUNPJFGIODEJLQ-UHFFFAOYSA-M potassium;2,2,2-trifluoroacetate Chemical compound [K+].[O-]C(=O)C(F)(F)F CUNPJFGIODEJLQ-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- XOVSRHHCHKUFKM-UHFFFAOYSA-N s-methylthiohydroxylamine Chemical compound CSN XOVSRHHCHKUFKM-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000004328 sodium tetraborate Substances 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- VSTSKETWEBYEHL-RITPCOANSA-N tert-butyl n-[(2r,3s)-2-methyl-4-oxoazetidin-3-yl]carbamate Chemical compound C[C@H]1NC(=O)[C@H]1NC(=O)OC(C)(C)C VSTSKETWEBYEHL-RITPCOANSA-N 0.000 description 1
- VSTSKETWEBYEHL-GDVGLLTNSA-N tert-butyl n-[(3s)-2-methyl-4-oxoazetidin-3-yl]carbamate Chemical compound CC1NC(=O)[C@H]1NC(=O)OC(C)(C)C VSTSKETWEBYEHL-GDVGLLTNSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/568—Four-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Cephalosporin Compounds (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Pyrrole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Saccharide Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24892981A | 1981-03-30 | 1981-03-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HU187685B true HU187685B (en) | 1986-02-28 |
Family
ID=22941310
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU82959A HU187685B (en) | 1981-03-30 | 1982-03-29 | Process for preparing 2-oxo-1-/substituted phosphinyl/-azetidines |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP0061765B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JPS57175196A (cg-RX-API-DMAC7.html) |
| AT (1) | ATE15205T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU557712B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA1202024A (cg-RX-API-DMAC7.html) |
| DE (1) | DE3265737D1 (cg-RX-API-DMAC7.html) |
| DK (1) | DK142782A (cg-RX-API-DMAC7.html) |
| ES (1) | ES510907A0 (cg-RX-API-DMAC7.html) |
| GR (1) | GR75925B (cg-RX-API-DMAC7.html) |
| HU (1) | HU187685B (cg-RX-API-DMAC7.html) |
| IE (1) | IE52837B1 (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ200155A (cg-RX-API-DMAC7.html) |
| PH (3) | PH19170A (cg-RX-API-DMAC7.html) |
| PT (1) | PT74672B (cg-RX-API-DMAC7.html) |
| ZA (1) | ZA822147B (cg-RX-API-DMAC7.html) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0088488B1 (en) * | 1982-01-22 | 1986-10-01 | Beecham Group Plc | Antibacterial agents, their preparation and use |
| EP0095394B1 (en) * | 1982-05-24 | 1986-12-10 | E.R. Squibb & Sons, Inc. | 2-oxo-1-(thiophosphonic or thiophosphinic)-azetidines |
| DE3475712D1 (de) * | 1983-05-31 | 1989-01-26 | Squibb & Sons Inc | Ûû(3-acylamino-2-oxo-1-azetidinyl)oxy¨methyl¨phosphinic acids |
| US4670554A (en) * | 1983-05-31 | 1987-06-02 | E. R. Squibb & Sons, Inc. | ((3-Acylamino-2-oxo-1-azetidinyl)oxy)methyl)phosphinic acids |
| US4587051A (en) * | 1983-07-18 | 1986-05-06 | E. R. Squibb & Sons, Inc. | Desulfonation process for preparing 2-azetidinones |
| EP0187500B1 (en) * | 1984-12-20 | 1993-04-28 | The Upjohn Company | Monobactams |
| US4883869A (en) * | 1984-12-20 | 1989-11-28 | The Upjohn Company | Novel beta-lactams containing amino acid substituents |
| US4723002A (en) * | 1986-04-28 | 1988-02-02 | E. R. Squibb & Sons, Inc. | 1-(substituted phosphorous)-azetidinone antibacterials |
| MY110249A (en) * | 1989-05-31 | 1998-03-31 | Univ Florida State | Method for preparation of taxol using beta lactam |
| US5284865A (en) * | 1991-09-23 | 1994-02-08 | Holton Robert A | Cyclohexyl substituted taxanes and pharmaceutical compositions containing them |
| KR950013578B1 (ko) * | 1993-04-10 | 1995-11-09 | 주식회사럭키 | 신규 티아(디아)졸 초산의 반응성 티오포스페이트 유도체 및 그의 제조방법 |
| BR0214277A (pt) | 2001-11-30 | 2004-09-21 | Bristol Myers Squibb Co | Solvatos de paclitaxel |
| EP2755983B1 (en) | 2011-09-12 | 2017-03-15 | Idenix Pharmaceuticals LLC. | Substituted carbonyloxymethylphosphoramidate compounds and pharmaceutical compositions for the treatment of viral infections |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3511635A (en) * | 1967-08-04 | 1970-05-12 | Ethyl Corp | Herbicidal organophosphorus-nitrogen compositions and method using same |
| DE3069832D1 (en) * | 1979-09-13 | 1985-01-31 | Kyowa Hakko Kogyo Kk | Acylated cephalosporin analogs, process for their preparation and pharmaceutical compositions comprising them |
-
1982
- 1982-03-29 GR GR67732A patent/GR75925B/el unknown
- 1982-03-29 AT AT82102646T patent/ATE15205T1/de not_active IP Right Cessation
- 1982-03-29 CA CA000399592A patent/CA1202024A/en not_active Expired
- 1982-03-29 ES ES510907A patent/ES510907A0/es active Granted
- 1982-03-29 PH PH27070A patent/PH19170A/en unknown
- 1982-03-29 ZA ZA822147A patent/ZA822147B/xx unknown
- 1982-03-29 NZ NZ200155A patent/NZ200155A/en unknown
- 1982-03-29 EP EP82102646A patent/EP0061765B1/en not_active Expired
- 1982-03-29 DE DE8282102646T patent/DE3265737D1/de not_active Expired
- 1982-03-29 PT PT74672A patent/PT74672B/pt not_active IP Right Cessation
- 1982-03-29 IE IE751/82A patent/IE52837B1/en not_active IP Right Cessation
- 1982-03-29 AU AU82126/82A patent/AU557712B2/en not_active Ceased
- 1982-03-29 HU HU82959A patent/HU187685B/hu not_active IP Right Cessation
- 1982-03-29 DK DK142782A patent/DK142782A/da not_active Application Discontinuation
- 1982-03-30 JP JP57052202A patent/JPS57175196A/ja active Granted
-
1984
- 1984-02-15 PH PH30251A patent/PH19181A/en unknown
- 1984-02-15 PH PH30252A patent/PH19664A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PH19664A (en) | 1986-06-09 |
| PH19181A (en) | 1986-01-23 |
| AU557712B2 (en) | 1987-01-08 |
| ES8305000A1 (es) | 1983-03-16 |
| PT74672A (en) | 1982-04-01 |
| EP0061765B1 (en) | 1985-08-28 |
| IE52837B1 (en) | 1988-03-16 |
| EP0061765A1 (en) | 1982-10-06 |
| ZA822147B (en) | 1983-02-23 |
| NZ200155A (en) | 1985-08-16 |
| ES510907A0 (es) | 1983-03-16 |
| JPS57175196A (en) | 1982-10-28 |
| PH19170A (en) | 1986-01-16 |
| CA1202024A (en) | 1986-03-18 |
| DK142782A (da) | 1982-10-01 |
| DE3265737D1 (en) | 1985-10-03 |
| PT74672B (en) | 1983-11-08 |
| AU8212682A (en) | 1982-10-07 |
| GR75925B (cg-RX-API-DMAC7.html) | 1984-08-02 |
| IE820751L (en) | 1982-09-30 |
| ATE15205T1 (de) | 1985-09-15 |
| JPH0451558B2 (cg-RX-API-DMAC7.html) | 1992-08-19 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HU90 | Patent valid on 900628 | ||
| HMM4 | Cancellation of final prot. due to non-payment of fee |