JP2008542376A - クラスＤのβラクタマーゼ阻害剤としての三環系６−アルキリデンペネム類 - Google Patents

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Publication number

JP2008542376A

JP2008542376A JP2008514712A JP2008514712A JP2008542376A JP 2008542376 A JP2008542376 A JP 2008542376A JP 2008514712 A JP2008514712 A JP 2008514712A JP 2008514712 A JP2008514712 A JP 2008514712A JP 2008542376 A JP2008542376 A JP 2008542376A

Authority

JP

Japan

Prior art keywords

optionally substituted

oxo

thia

azabicyclo

ene

Prior art date

2005-06-01

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Withdrawn

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• 239000003781 beta lactamase inhibitor Substances 0.000 title description 8
• 229940126813 beta-lactamase inhibitor Drugs 0.000 title description 8
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 77
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 60
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 58
• 150000001875 compounds Chemical class 0.000 claims abstract description 57
• 239000003782 beta lactam antibiotic agent Substances 0.000 claims abstract description 20
• 239000002132 β-lactam antibiotic Substances 0.000 claims abstract description 20
• 229940124586 β-lactam antibiotics Drugs 0.000 claims abstract description 20
• 102000004190 Enzymes Human genes 0.000 claims abstract description 16
• 108090000790 Enzymes Proteins 0.000 claims abstract description 16
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 15
• 239000001257 hydrogen Substances 0.000 claims abstract description 13
• 208000035143 Bacterial infection Diseases 0.000 claims abstract description 8
• 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 8
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
• 238000000034 method Methods 0.000 claims description 226
• -1 substituted Chemical class 0.000 claims description 139
• 229910052799 carbon Inorganic materials 0.000 claims description 70
• 125000003118 aryl group Chemical group 0.000 claims description 48
• 229910052757 nitrogen Inorganic materials 0.000 claims description 46
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 44
• 159000000000 sodium salts Chemical class 0.000 claims description 40
• 150000001721 carbon Chemical group 0.000 claims description 35
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 35
• NPDLYUOYAGBHFB-WDSKDSINSA-N Asn-Arg Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N NPDLYUOYAGBHFB-WDSKDSINSA-N 0.000 claims description 34
• 125000000217 alkyl group Chemical group 0.000 claims description 34
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 30
• FYZUENZXIZCLAZ-UHFFFAOYSA-N 2-methylhept-2-enoic acid Chemical compound CCCCC=C(C)C(O)=O FYZUENZXIZCLAZ-UHFFFAOYSA-N 0.000 claims description 30
• 229920006395 saturated elastomer Polymers 0.000 claims description 26
• 125000005842 heteroatom Chemical group 0.000 claims description 21
• 230000015572 biosynthetic process Effects 0.000 claims description 18
• 125000004432 carbon atom Chemical group C* 0.000 claims description 16
• 125000000623 heterocyclic group Chemical group 0.000 claims description 16
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
• 239000000126 substance Substances 0.000 claims description 15
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 12
• 125000003342 alkenyl group Chemical group 0.000 claims description 11
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
• 125000003003 spiro group Chemical group 0.000 claims description 11
• 125000003107 substituted aryl group Chemical group 0.000 claims description 11
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 10
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 8
• 229910052736 halogen Inorganic materials 0.000 claims description 8
• 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 7
• 150000002148 esters Chemical class 0.000 claims description 7
• 125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 7
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
• 150000002367 halogens Chemical class 0.000 claims description 6
• 125000002950 monocyclic group Chemical group 0.000 claims description 6
• 150000003839 salts Chemical class 0.000 claims description 6
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
• 125000004104 aryloxy group Chemical group 0.000 claims description 5
• 125000005018 aryl alkenyl group Chemical group 0.000 claims description 4
• 125000005325 aryloxy aryl group Chemical group 0.000 claims description 4
• 125000002619 bicyclic group Chemical group 0.000 claims description 4
• 125000004122 cyclic group Chemical group 0.000 claims description 4
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
• 238000001727 in vivo Methods 0.000 claims description 4
• 230000002401 inhibitory effect Effects 0.000 claims description 4
• 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 4
• GRYKCKSOHDCZJF-YLBKJFSISA-N (5r,6z)-7-oxo-6-(4h-thieno[2,3]thiopyrano[2,4-b]pyridin-2-ylmethylidene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1SC2=NC=CC=C2C(S2)=C1C=C2/C=C1/C(=O)N2[C@@H]1SC=C2C(=O)O GRYKCKSOHDCZJF-YLBKJFSISA-N 0.000 claims description 3
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 3
• 125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
• 125000005133 alkynyloxy group Chemical group 0.000 claims description 3
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 3
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
• RLYFCCSEWJKCQN-LEPFTWFBSA-N chembl1162147 Chemical compound C1OCCC2=C1OC1=CC(/C=C3/C(=O)N4[C@@H]3SC=C4C(=O)O)=NN12 RLYFCCSEWJKCQN-LEPFTWFBSA-N 0.000 claims description 3
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 3
• 125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
• RITQDZWBRPLXHO-NUZRTGFDSA-N (5R,6Z)-7-oxo-6-[[7-(2-phenylmethoxyethoxy)-1,8,10-triazatricyclo[7.3.0.02,6]dodeca-2(6),7,9,11-tetraen-11-yl]methylidene]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1([C@@H]2SC=C1C(=O)O)C(=O)\C2=C\C(N=C1N=2)=CN1C=1CCCC=1C=2OCCOCC1=CC=CC=C1 RITQDZWBRPLXHO-NUZRTGFDSA-N 0.000 claims description 2
• AHICGCNKVSGCLQ-WSVPDTOYSA-N (5r,6z)-7-oxo-6-(spiro[1,3-dioxolane-2,7'-8,9-dihydro-6h-[1,2,4]triazolo[1,5-a]quinazoline]-2'-ylmethylidene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1([C@@H]2SC=C1C(=O)O)C(=O)\C2=C\C(=NN1C=2CC3)N=C1N=CC=2CC13OCCO1 AHICGCNKVSGCLQ-WSVPDTOYSA-N 0.000 claims description 2
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 2
• OWKFKAWHZKUXBM-WSVPDTOYSA-N (5R,6Z)-6-[(7-methoxy-1,8,10-triazatricyclo[7.3.0.02,6]dodeca-2(6),7,9,11-tetraen-11-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound COC1=NC2=NC(\C=C/3C(N4C(=CS[C@@H]4\3)C(O)=O)=O)=CN2C2=C1CCC2 OWKFKAWHZKUXBM-WSVPDTOYSA-N 0.000 claims 1
• LVDAGEHCAGXUMS-VYLZPFMQSA-N (5R,6Z)-7-oxo-6-([1,3]thiazolo[3,2-a]benzimidazol-2-ylmethylidene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound S1C2=NC3=CC=CC=C3N2C=C1/C=C1/C(=O)N2[C@@H]1SC=C2C(=O)O LVDAGEHCAGXUMS-VYLZPFMQSA-N 0.000 claims 1
• FNBVVWRNKCSCSF-JKLGPDONSA-N (5r,6e)-6-[(5-benzyl-6-oxobenzo[b][1,4]benzoxazepin-3-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1([C@@H]2SC=C1C(=O)O)C(=O)\C2=C/C(C=C12)=CC=C1OC1=CC=CC=C1C(=O)N2CC1=CC=CC=C1 FNBVVWRNKCSCSF-JKLGPDONSA-N 0.000 claims 1
• ZMVPSTWCZFOKMA-VYLZPFMQSA-N (5r,6z)-6-(1,2-dihydro-[1,3]thiazolo[3,2-a]benzimidazol-7-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1([C@@H]2SC=C1C(=O)O)C(=O)\C2=C\C(C=C12)=CC=C1N=C1N2CCS1 ZMVPSTWCZFOKMA-VYLZPFMQSA-N 0.000 claims 1
• UIEWFJZVZVDQLA-IZIDJEDMSA-N (5r,6z)-6-(3,4-dihydro-2h-[1,3]thiazino[3,2-a]benzimidazol-7-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound S1CCCN2C3=CC(/C=C4/C(=O)N5[C@@H]4SC=C5C(=O)O)=CC=C3N=C21 UIEWFJZVZVDQLA-IZIDJEDMSA-N 0.000 claims 1
• SBFSPMJWFBHKNG-UUKWBXHYSA-N (5r,6z)-6-(imidazo[1,2-a]quinolin-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1=C2C=CC3=CC=CC=C3N2C=C1/C=C1/C(=O)N2[C@@H]1SC=C2C(=O)O SBFSPMJWFBHKNG-UUKWBXHYSA-N 0.000 claims 1
• SWNURUJCQSUVHE-MGDKSHQASA-N (5r,6z)-6-(imidazo[1,2-a]quinoxalin-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1=C2C=NC3=CC=CC=C3N2C=C1/C=C1/C(=O)N2[C@@H]1SC=C2C(=O)O SWNURUJCQSUVHE-MGDKSHQASA-N 0.000 claims 1
• ZQZVENIYZGCSFN-VYLZPFMQSA-N (5r,6z)-6-(imidazo[2,1-b][1,3]benzothiazol-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1=C2SC3=CC=CC=C3N2C=C1/C=C1/C(=O)N2[C@@H]1SC=C2C(=O)O ZQZVENIYZGCSFN-VYLZPFMQSA-N 0.000 claims 1
• VOFYPSOWJHHFAS-IZIDJEDMSA-N (5r,6z)-6-[(5-methyl-6,7,8,9-tetrahydro-[1,2,4]triazolo[1,5-a]quinazolin-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1CCCC2=C1N1N=C(\C=C/3C(N4C(=CS[C@@H]4\3)C(O)=O)=O)N=C1N=C2C VOFYPSOWJHHFAS-IZIDJEDMSA-N 0.000 claims 1
• GVIJNDBUPIEBNV-VYLZPFMQSA-N (5r,6z)-6-[(5-methyl-7,8-dihydro-6h-cyclopenta[e][1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methylene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound CC1=NC2=NC(\C=C/3C(N4C(=CS[C@@H]4\3)C(O)=O)=O)=NN2C2=C1CCC2 GVIJNDBUPIEBNV-VYLZPFMQSA-N 0.000 claims 1
• IAUJWOFPTCUPKI-WSVPDTOYSA-N (5r,6z)-6-{[7-(ethoxycarbonyl)-6,7,8,9-tetrahydropyrido[3,4-e][1,2,4]triazolo[1,5-a]pyrimidin-2-yl]methylene}-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1=NC2=NC(\C=C/3C(N4C(=CS[C@@H]4\3)C(O)=O)=O)=NN2C2=C1CN(C(=O)OCC)CC2 IAUJWOFPTCUPKI-WSVPDTOYSA-N 0.000 claims 1
• WBVGDYUBKRMKNU-HMZQOCAUSA-N (5r,6z)-7-oxo-6-(5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]benzoxazol-2-ylmethylidene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1CCCC2=C1OC1=CC(/C=C3/C(=O)N4[C@@H]3SC=C4C(=O)O)=NN12 WBVGDYUBKRMKNU-HMZQOCAUSA-N 0.000 claims 1
• YJHLAPIOTYDKSI-VYLZPFMQSA-N (5r,6z)-7-oxo-6-([1,3]thiazolo[3,2-a]benzimidazol-7-ylmethylidene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1([C@@H]2SC=C1C(=O)O)C(=O)\C2=C\C(C=C12)=CC=C1N=C1N2C=CS1 YJHLAPIOTYDKSI-VYLZPFMQSA-N 0.000 claims 1
• TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 claims 1
• 150000003973 alkyl amines Chemical class 0.000 claims 1
• XFARUGBBAMTOCU-IBSXUBTNSA-N chembl1205614 Chemical compound C1CCC(SC2=N3)=C1N2C=C3/C=C1/C(=O)N2[C@@H]1SC=C2C(=O)O XFARUGBBAMTOCU-IBSXUBTNSA-N 0.000 claims 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• GDDZRTPUGYRYNK-IZRWNGHKSA-M sodium;(5r,6z)-7-oxo-6-(5,6,7,8-tetrahydroimidazo[1,2][1,2,4]triazolo[2,4-a]pyridin-2-ylmethylidene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound [Na+].C1CCCC2=NC3=NC(/C=C4/C(=O)N5[C@@H]4SC=C5C(=O)[O-])=CN3N21 GDDZRTPUGYRYNK-IZRWNGHKSA-M 0.000 claims 1
• 125000004426 substituted alkynyl group Chemical group 0.000 claims 1
• 102000006635 beta-lactamase Human genes 0.000 abstract description 10
• 108090000204 Dipeptidase 1 Proteins 0.000 abstract description 4
• 206010034133 Pathogen resistance Diseases 0.000 abstract description 4
• 239000003112 inhibitor Substances 0.000 abstract description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 445
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 300
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 212
• 239000011541 reaction mixture Substances 0.000 description 186
• 235000019439 ethyl acetate Nutrition 0.000 description 150
• 239000000203 mixture Substances 0.000 description 130
• 239000000243 solution Substances 0.000 description 121
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 118
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
• 238000002360 preparation method Methods 0.000 description 113
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 111
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 108
• 239000007787 solid Substances 0.000 description 108
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 99
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 90
• 239000000047 product Substances 0.000 description 88
• 230000002829 reductive effect Effects 0.000 description 72
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 67
• 239000012044 organic layer Substances 0.000 description 66
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 63
• 239000000706 filtrate Substances 0.000 description 61
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 60
• 239000010410 layer Substances 0.000 description 58
• 238000006243 chemical reaction Methods 0.000 description 55
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
• 238000005160 1H NMR spectroscopy Methods 0.000 description 49
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 40
• 239000011888 foil Substances 0.000 description 40
• 239000012267 brine Substances 0.000 description 39
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 39
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 35
• 239000008363 phosphate buffer Substances 0.000 description 34
• 239000002244 precipitate Substances 0.000 description 33
• 125000001424 substituent group Chemical group 0.000 description 32
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 31
• 238000010898 silica gel chromatography Methods 0.000 description 28
• 238000004440 column chromatography Methods 0.000 description 26
• 239000013078 crystal Substances 0.000 description 26
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 26
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
• 238000001816 cooling Methods 0.000 description 22
• 239000011734 sodium Substances 0.000 description 22
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 21
• 235000019341 magnesium sulphate Nutrition 0.000 description 21
• 230000002441 reversible effect Effects 0.000 description 21
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 20
• 238000000746 purification Methods 0.000 description 20
• 229920005989 resin Polymers 0.000 description 20
• 239000011347 resin Substances 0.000 description 20
• 239000012300 argon atmosphere Substances 0.000 description 19
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• 239000008367 deionised water Substances 0.000 description 18
• 229910021641 deionized water Inorganic materials 0.000 description 18
• 239000000741 silica gel Substances 0.000 description 17
• 229910002027 silica gel Inorganic materials 0.000 description 17
• 239000007858 starting material Substances 0.000 description 17
• 239000003921 oil Substances 0.000 description 16
• BCQLGSCBQKKBIM-CMPLNLGQSA-N (4-nitrophenyl)methyl (5r,6s)-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)C1=CS[C@H]2N1C(=O)[C@@H]2Br BCQLGSCBQKKBIM-CMPLNLGQSA-N 0.000 description 15
• 238000001914 filtration Methods 0.000 description 15
• 239000012429 reaction media Substances 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• 239000000428 dust Substances 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
• 239000000460 chlorine Substances 0.000 description 12
• 239000002274 desiccant Substances 0.000 description 12
• 229910052938 sodium sulfate Inorganic materials 0.000 description 12
• 235000011152 sodium sulphate Nutrition 0.000 description 12
• 238000005481 NMR spectroscopy Methods 0.000 description 11
• 150000001299 aldehydes Chemical class 0.000 description 10
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 10
• 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 10
• 239000000725 suspension Substances 0.000 description 10
• 125000000304 alkynyl group Chemical group 0.000 description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 8
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
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