UA78047C2 - A process for preparation of 6-alkylidene penem derivatives - Google Patents
A process for preparation of 6-alkylidene penem derivatives Download PDFInfo
- Publication number
- UA78047C2 UA78047C2 UA20041109834A UA20041109834A UA78047C2 UA 78047 C2 UA78047 C2 UA 78047C2 UA 20041109834 A UA20041109834 A UA 20041109834A UA 20041109834 A UA20041109834 A UA 20041109834A UA 78047 C2 UA78047 C2 UA 78047C2
- Authority
- UA
- Ukraine
- Prior art keywords
- optionally substituted
- alkyl
- solution
- mixture
- nitrobenzyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 92
- 230000008569 process Effects 0.000 title abstract description 4
- 238000002360 preparation method Methods 0.000 title description 64
- 150000001875 compounds Chemical class 0.000 claims abstract description 145
- 239000000203 mixture Substances 0.000 claims description 341
- 239000011541 reaction mixture Substances 0.000 claims description 246
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 161
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 156
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 136
- 238000006243 chemical reaction Methods 0.000 claims description 116
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 91
- 125000001072 heteroaryl group Chemical group 0.000 claims description 79
- 229910052799 carbon Inorganic materials 0.000 claims description 64
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 60
- 239000008363 phosphate buffer Substances 0.000 claims description 56
- 125000004432 carbon atom Chemical group C* 0.000 claims description 52
- 125000003118 aryl group Chemical group 0.000 claims description 51
- -1 substituted Chemical class 0.000 claims description 51
- 229920006395 saturated elastomer Polymers 0.000 claims description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 125000000217 alkyl group Chemical group 0.000 claims description 34
- 125000001424 substituent group Chemical group 0.000 claims description 34
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 33
- 125000005842 heteroatom Chemical group 0.000 claims description 29
- 125000002619 bicyclic group Chemical group 0.000 claims description 28
- 125000004122 cyclic group Chemical group 0.000 claims description 27
- 230000015572 biosynthetic process Effects 0.000 claims description 26
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 26
- 239000003960 organic solvent Substances 0.000 claims description 25
- HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 claims description 24
- 125000003107 substituted aryl group Chemical group 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
- YXIWHUQXZSMYRE-UHFFFAOYSA-N 1,3-benzothiazole-2-thiol Chemical compound C1=CC=C2SC(S)=NC2=C1 YXIWHUQXZSMYRE-UHFFFAOYSA-N 0.000 claims description 16
- 150000001299 aldehydes Chemical class 0.000 claims description 15
- 230000003993 interaction Effects 0.000 claims description 15
- 125000002950 monocyclic group Chemical group 0.000 claims description 15
- 238000010992 reflux Methods 0.000 claims description 15
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 13
- 238000006894 reductive elimination reaction Methods 0.000 claims description 13
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 12
- 238000009835 boiling Methods 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 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 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 11
- 125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- 230000009471 action Effects 0.000 claims description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 229910052708 sodium Inorganic materials 0.000 claims description 9
- 230000009466 transformation Effects 0.000 claims description 9
- MCNQUWLLXZZZAC-UHFFFAOYSA-N 4-cyano-1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-n-piperidin-1-ylpyrazole-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=C(C#N)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl MCNQUWLLXZZZAC-UHFFFAOYSA-N 0.000 claims description 8
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 8
- 125000005325 aryloxy aryl group Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 claims description 7
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 7
- 239000002841 Lewis acid Substances 0.000 claims description 7
- 239000002635 aromatic organic solvent Substances 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 7
- 150000007517 lewis acids Chemical class 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 150000007524 organic acids Chemical class 0.000 claims description 7
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Substances [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 7
- VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 claims description 6
- 229910052770 Uranium Inorganic materials 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 6
- 238000005984 hydrogenation reaction Methods 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 5
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 5
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 235000010288 sodium nitrite Nutrition 0.000 claims description 5
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- 239000003849 aromatic solvent Substances 0.000 claims description 4
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 4
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 claims description 4
- 229940125833 compound 23 Drugs 0.000 claims description 4
- 238000009833 condensation Methods 0.000 claims description 4
- 230000005494 condensation Effects 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 4
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 claims description 4
- 125000005010 perfluoroalkyl group Chemical class 0.000 claims description 4
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims description 4
- 239000008096 xylene Substances 0.000 claims description 4
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 claims description 3
- AZFNGPAYDKGCRB-XCPIVNJJSA-M [(1s,2s)-2-amino-1,2-diphenylethyl]-(4-methylphenyl)sulfonylazanide;chlororuthenium(1+);1-methyl-4-propan-2-ylbenzene Chemical compound [Ru+]Cl.CC(C)C1=CC=C(C)C=C1.C1=CC(C)=CC=C1S(=O)(=O)[N-][C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 AZFNGPAYDKGCRB-XCPIVNJJSA-M 0.000 claims description 3
- 150000008065 acid anhydrides Chemical class 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 claims description 3
- 239000004304 potassium nitrite Substances 0.000 claims description 3
- 235000010289 potassium nitrite Nutrition 0.000 claims description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 3
- 150000003751 zinc Chemical class 0.000 claims description 3
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 2
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims 29
- SDGCXMDTXHFBPH-SDMSXHDGSA-N (5r)-6-bromo-4-thia-1-azabicyclo[3.2.0]hept-2-en-7-one Chemical class S1C=CN2C(=O)C(Br)[C@H]21 SDGCXMDTXHFBPH-SDMSXHDGSA-N 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 235000020028 corn beer Nutrition 0.000 claims 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000003003 spiro group Chemical group 0.000 claims 1
- 238000012876 topography Methods 0.000 claims 1
- 208000035143 Bacterial infection Diseases 0.000 abstract description 3
- 208000022362 bacterial infectious disease Diseases 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 505
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 369
- 239000000243 solution Substances 0.000 description 363
- 235000019439 ethyl acetate Nutrition 0.000 description 169
- 239000010410 layer Substances 0.000 description 168
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 149
- 239000007787 solid Substances 0.000 description 144
- 230000002829 reductive effect Effects 0.000 description 129
- 239000012044 organic layer Substances 0.000 description 122
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 115
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 107
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 104
- 239000000706 filtrate Substances 0.000 description 93
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 92
- 239000000047 product Substances 0.000 description 92
- FYZUENZXIZCLAZ-UHFFFAOYSA-N 2-methylhept-2-enoic acid Chemical compound CCCCC=C(C)C(O)=O FYZUENZXIZCLAZ-UHFFFAOYSA-N 0.000 description 82
- VJJRVNGOHNKPHB-UHFFFAOYSA-N 1-nitro-4-[(4-nitrophenyl)methoxymethyl]benzene Chemical compound C1=CC([N+](=O)[O-])=CC=C1COCC1=CC=C([N+]([O-])=O)C=C1 VJJRVNGOHNKPHB-UHFFFAOYSA-N 0.000 description 80
- 239000000741 silica gel Substances 0.000 description 77
- 229910002027 silica gel Inorganic materials 0.000 description 77
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 70
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 68
- 239000011888 foil Substances 0.000 description 68
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 66
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
- 159000000000 sodium salts Chemical class 0.000 description 60
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 58
- 239000012299 nitrogen atmosphere Substances 0.000 description 47
- 238000010828 elution Methods 0.000 description 38
- 239000007864 aqueous solution Substances 0.000 description 37
- 239000000126 substance Substances 0.000 description 33
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 32
- 238000003756 stirring Methods 0.000 description 32
- 239000011347 resin Substances 0.000 description 28
- 229920005989 resin Polymers 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000013078 crystal Substances 0.000 description 26
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 25
- 239000012141 concentrate Substances 0.000 description 25
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 22
- 239000003921 oil Substances 0.000 description 22
- 235000019198 oils Nutrition 0.000 description 22
- 238000001179 sorption measurement Methods 0.000 description 22
- 239000002244 precipitate Substances 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 239000000843 powder Substances 0.000 description 20
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 19
- 238000001816 cooling Methods 0.000 description 18
- 239000012047 saturated solution Substances 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
- IOJUPLGTWVMSFF-UHFFFAOYSA-N cyclobenzothiazole Natural products C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 17
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 16
- 239000000428 dust Substances 0.000 description 16
- HHXMXAQDOUCLDN-RXMQYKEDSA-N penem Chemical compound S1C=CN2C(=O)C[C@H]21 HHXMXAQDOUCLDN-RXMQYKEDSA-N 0.000 description 16
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 16
- 235000017557 sodium bicarbonate Nutrition 0.000 description 16
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
- 229910052938 sodium sulfate Inorganic materials 0.000 description 16
- 235000011152 sodium sulphate Nutrition 0.000 description 16
- 239000003480 eluent Substances 0.000 description 15
- 150000002431 hydrogen Chemical class 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 239000012300 argon atmosphere Substances 0.000 description 13
- 239000002585 base Substances 0.000 description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 12
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- 235000011181 potassium carbonates Nutrition 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 11
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- 238000000354 decomposition reaction Methods 0.000 description 9
- 239000008367 deionised water Substances 0.000 description 9
- 229910021641 deionized water Inorganic materials 0.000 description 9
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- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 1
- 239000012262 resinous product Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- SETMGIIITGNLAS-UHFFFAOYSA-N spizofurone Chemical compound O=C1C2=CC(C(=O)C)=CC=C2OC21CC2 SETMGIIITGNLAS-UHFFFAOYSA-N 0.000 description 1
- 229950001870 spizofurone Drugs 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- OVRJVKCZJCNSOW-UHFFFAOYSA-N thian-4-one Chemical compound O=C1CCSCC1 OVRJVKCZJCNSOW-UHFFFAOYSA-N 0.000 description 1
- BKWCJIGGAIADBJ-UHFFFAOYSA-N thiazine-2-carboxylic acid Chemical compound OC(=O)N1SC=CC=C1 BKWCJIGGAIADBJ-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- OHKOGUYZJXTSFX-KZFFXBSXSA-N ticarcillin Chemical compound C=1([C@@H](C(O)=O)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)C=CSC=1 OHKOGUYZJXTSFX-KZFFXBSXSA-N 0.000 description 1
- 229960004659 ticarcillin Drugs 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- HYEGLMPHWGFMSN-UHFFFAOYSA-N trifluoromethanesulfonic acid;trifluoromethylsulfonyl trifluoromethanesulfonate Chemical compound OS(=O)(=O)C(F)(F)F.FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F HYEGLMPHWGFMSN-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/88—Compounds with a double bond between positions 2 and 3 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D499/881—Compounds with a double bond between positions 2 and 3 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with a hydrogen atom or an unsubstituted hydrocarbon radical, attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/88—Compounds with a double bond between positions 2 and 3 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37704802P | 2002-05-01 | 2002-05-01 | |
| PCT/US2003/013429 WO2003093277A1 (en) | 2002-05-01 | 2003-04-30 | Process for preparing 6-alkylidene penem derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA78047C2 true UA78047C2 (en) | 2007-02-15 |
Family
ID=29401435
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA20041109834A UA78047C2 (en) | 2002-05-01 | 2003-04-30 | A process for preparation of 6-alkylidene penem derivatives |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US20040053913A1 (no) |
| EP (1) | EP1499620B1 (no) |
| JP (1) | JP2005523937A (no) |
| KR (1) | KR20050007369A (no) |
| CN (1) | CN100516069C (no) |
| AR (1) | AR039476A1 (no) |
| AT (1) | ATE456569T1 (no) |
| AU (2) | AU2003228773A1 (no) |
| BR (1) | BR0309753A (no) |
| CA (1) | CA2483533A1 (no) |
| CR (1) | CR7512A (no) |
| DE (1) | DE60331138D1 (no) |
| EC (1) | ECSP045396A (no) |
| IL (1) | IL164900A0 (no) |
| MX (1) | MXPA04010661A (no) |
| NO (1) | NO20044548L (no) |
| NZ (1) | NZ536183A (no) |
| RU (1) | RU2317297C2 (no) |
| SG (1) | SG165159A1 (no) |
| TW (1) | TW200403248A (no) |
| UA (1) | UA78047C2 (no) |
| WO (1) | WO2003093277A1 (no) |
| ZA (1) | ZA200409687B (no) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR039774A1 (es) * | 2002-05-01 | 2005-03-02 | Wyeth Corp | 6-alquiliden-penems biciclicos como inhibidores de beta-lactamasas |
| US20040132708A1 (en) * | 2002-05-01 | 2004-07-08 | Wyeth | Process for preparing 6-alkylidene penem derivatives |
| AR039475A1 (es) * | 2002-05-01 | 2005-02-23 | Wyeth Corp | 6-alquiliden-penems triciclicos como inhibidores de beta-lactamasa |
| JP2007501635A (ja) * | 2003-05-16 | 2007-02-01 | ワイス・ホールディングズ・コーポレイション | β−ラクタマーゼ阻害剤中間体を合成するための方法 |
| TW200716104A (en) * | 2005-06-01 | 2007-05-01 | Wyeth Corp | Tricyclic 6-alkylidene-penems as class-D β -lactamases inhibitors |
| TW200716102A (en) * | 2005-06-01 | 2007-05-01 | Wyeth Corp | Bicyclic 6-alkylidene-penems as class-D β -lactamases inhibitors |
| KR20080032637A (ko) * | 2005-07-27 | 2008-04-15 | 와이어쓰 | 이환식 6-알킬리덴-페넴 β-락타마제 저해제 및 β-락탐항생제 조합: 광범위 항생제 |
| WO2007027323A2 (en) * | 2005-07-27 | 2007-03-08 | Wyeth | TRICYCLIC 6-ALKYLIDENE-PENEM β-LACTAMASE INHIBITORS AND β-LACTAM ANTIBIOTIC COMBINATION: A BROAD SPECTRUM ANTIBIOTIC |
| GT200600380A (es) * | 2005-08-24 | 2007-03-29 | Proceso para la preparacion de inhibidores de beta-lactamasa | |
| US20090018332A1 (en) * | 2007-06-28 | 2009-01-15 | Wyeth | Processes For Preparing Bicyclic Oxazine Carboxaldehyde and Beta-Lactamase Inhibitors |
| US20100063023A1 (en) * | 2008-09-10 | 2010-03-11 | Wyeth | Bicyclic and Tricyclic Substituted 6-Methylidene Carbapenems as Broad Spectrum Beta-Lactamase Inhibitors |
| CN102020615B (zh) * | 2009-09-11 | 2012-08-29 | 中国中化股份有限公司 | 一种吗啉酮衍生物及其制备方法 |
| CN102020658B (zh) * | 2009-09-11 | 2012-05-23 | 中国中化股份有限公司 | 2-氯-6，8-二氢-5H-咪唑[2，1-c]-[1，4]噁嗪及其制备方法 |
| US20110288063A1 (en) * | 2010-05-19 | 2011-11-24 | Naeja Pharmaceutical Inc. | Novel fused bridged bicyclic heteroaryl substituted 6-alkylidene penems as potent beta-lactamase inhibitors |
| MX354745B (es) | 2012-09-25 | 2018-03-16 | Bayer Cropscience Ag | 3-fenilisoxazolin-5-carboxamidas 5-oxi-sustituidas y 3-fenilisoxazolin-5-tioamidas 5-oxi-sustituidas herbicidas y fungicidas. |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4206067A (en) * | 1978-10-02 | 1980-06-03 | Chevron Research Company | Thermally stabilized erosion-inhibited functional fluids containing perhalometal compounds and an organic base |
| GB8518416D0 (en) * | 1985-07-22 | 1985-08-29 | Beecham Group Plc | Compounds |
| EP0232966B1 (en) * | 1986-01-17 | 1997-10-08 | Beecham Group Plc | Process for the preparation of penem compounds and intermediates for this preparation |
| US4891369A (en) * | 1986-12-03 | 1990-01-02 | Taiho Pharmaceutical Company, Limited | 2β-Substituted-methylpenicillanic acid derivatives, and salts and esters thereof |
| US4977256A (en) * | 1987-12-07 | 1990-12-11 | Lederle (Japan), Ltd. | Method of eliminating protective groups |
| GB8729613D0 (en) * | 1987-12-18 | 1988-02-03 | Beecham Group Plc | Novel compounds |
| GB9222700D0 (en) * | 1992-10-29 | 1992-12-09 | Smithkline Beecham Plc | Chemical compounds |
| WO1995028935A1 (en) * | 1994-04-25 | 1995-11-02 | Smithkline Beecham Plc | Pharmaceutical formulations containing a beta-lactamase inhibiting penem in combination with a beta-lactam antibiotic and their use in the treatment of bacterial infections |
| CA2346813A1 (en) * | 1998-10-15 | 2000-04-20 | Sarawak Medichem Pharmaceuticals Incorporated | Method and composition for treating and preventing tuberculosis |
| GB9928290D0 (en) * | 1999-12-01 | 2000-01-26 | Univ Belfast | Process for preparing ambient temperature ionic liquids |
| US20040132708A1 (en) * | 2002-05-01 | 2004-07-08 | Wyeth | Process for preparing 6-alkylidene penem derivatives |
| AR039475A1 (es) * | 2002-05-01 | 2005-02-23 | Wyeth Corp | 6-alquiliden-penems triciclicos como inhibidores de beta-lactamasa |
| AR039774A1 (es) * | 2002-05-01 | 2005-03-02 | Wyeth Corp | 6-alquiliden-penems biciclicos como inhibidores de beta-lactamasas |
| AR046041A1 (es) * | 2003-10-03 | 2005-11-23 | Aventis Pharma Inc | Procedimiento para la preparacion de compuestos heterociclicos n-amino sustituidos |
-
2003
- 2003-04-28 AR ARP030101470A patent/AR039476A1/es not_active Application Discontinuation
- 2003-04-29 TW TW092110032A patent/TW200403248A/zh unknown
- 2003-04-30 CA CA002483533A patent/CA2483533A1/en not_active Abandoned
- 2003-04-30 SG SG200607463-7A patent/SG165159A1/en unknown
- 2003-04-30 AT AT03726543T patent/ATE456569T1/de not_active IP Right Cessation
- 2003-04-30 RU RU2004135088/04A patent/RU2317297C2/ru not_active IP Right Cessation
- 2003-04-30 NZ NZ536183A patent/NZ536183A/en unknown
- 2003-04-30 BR BR0309753-6A patent/BR0309753A/pt not_active IP Right Cessation
- 2003-04-30 WO PCT/US2003/013429 patent/WO2003093277A1/en active Application Filing
- 2003-04-30 DE DE60331138T patent/DE60331138D1/de not_active Expired - Fee Related
- 2003-04-30 AU AU2003228773A patent/AU2003228773A1/en not_active Abandoned
- 2003-04-30 EP EP03726543A patent/EP1499620B1/en not_active Expired - Lifetime
- 2003-04-30 UA UA20041109834A patent/UA78047C2/uk unknown
- 2003-04-30 JP JP2004501416A patent/JP2005523937A/ja not_active Ceased
- 2003-04-30 KR KR10-2004-7017602A patent/KR20050007369A/ko not_active Application Discontinuation
- 2003-04-30 MX MXPA04010661A patent/MXPA04010661A/es active IP Right Grant
- 2003-04-30 CN CNB038096951A patent/CN100516069C/zh not_active Expired - Fee Related
- 2003-05-01 US US10/427,666 patent/US20040053913A1/en not_active Abandoned
-
2004
- 2004-10-06 CR CR7512A patent/CR7512A/es unknown
- 2004-10-22 NO NO20044548A patent/NO20044548L/no not_active Application Discontinuation
- 2004-10-28 IL IL16490004A patent/IL164900A0/xx unknown
- 2004-10-29 EC EC2004005396A patent/ECSP045396A/es unknown
- 2004-11-30 ZA ZA200409687A patent/ZA200409687B/xx unknown
-
2010
- 2010-03-11 AU AU2010200930A patent/AU2010200930A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AR039476A1 (es) | 2005-02-23 |
| ATE456569T1 (de) | 2010-02-15 |
| TW200403248A (en) | 2004-03-01 |
| WO2003093277A1 (en) | 2003-11-13 |
| EP1499620B1 (en) | 2010-01-27 |
| MXPA04010661A (es) | 2005-01-25 |
| US20040053913A1 (en) | 2004-03-18 |
| AU2010200930A1 (en) | 2010-04-01 |
| RU2004135088A (ru) | 2006-01-20 |
| CN1649881A (zh) | 2005-08-03 |
| AU2003228773A1 (en) | 2003-11-17 |
| CN100516069C (zh) | 2009-07-22 |
| NZ536183A (en) | 2006-07-28 |
| IL164900A0 (en) | 2005-12-18 |
| CR7512A (es) | 2005-01-05 |
| JP2005523937A (ja) | 2005-08-11 |
| ZA200409687B (en) | 2009-02-25 |
| KR20050007369A (ko) | 2005-01-17 |
| NO20044548L (no) | 2004-11-26 |
| EP1499620A1 (en) | 2005-01-26 |
| CA2483533A1 (en) | 2003-11-13 |
| SG165159A1 (en) | 2010-10-28 |
| BR0309753A (pt) | 2005-03-08 |
| DE60331138D1 (de) | 2010-03-18 |
| RU2317297C2 (ru) | 2008-02-20 |
| ECSP045396A (es) | 2005-01-03 |
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