CA1268183C - Intermediaires du phosphorane utilises dans la preparation de penems antibiotiques - Google Patents

Intermediaires du phosphorane utilises dans la preparation de penems antibiotiques

Info

Publication number: CA1268183C
Authority: CA; Canada
Prior art keywords: alkyl; phenyl; alkylamino; heterocyclic; amino
Prior art date: 1978-12-18
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.): Expired

Application number

CA423146

Other languages

English (en)

Inventor

Marcel Menard

Alain Martel

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bristol Myers Squibb Co

Original Assignee

Bristol Myers Co

Priority date (The priority date 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 date listed.)

1978-12-18

Filing date

1979-12-17

Publication date

1990-04-25

1979-12-17 Application filed by Bristol Myers Co filed Critical Bristol Myers Co

1990-04-25 Application granted granted Critical

1990-04-25 Publication of CA1268183C publication Critical patent/CA1268183C/fr

Status Expired legal-status Critical Current

Links

HHXMXAQDOUCLDN-RXMQYKEDSA-N penem Chemical compound S1C=CN2C(=O)C[C@H]21 HHXMXAQDOUCLDN-RXMQYKEDSA-N 0.000 title claims description 18
239000000543 intermediate Substances 0.000 title abstract description 19
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 title description 48
239000003242 anti bacterial agent Substances 0.000 title description 3
229940088710 antibiotic agent Drugs 0.000 title 1
125000000217 alkyl group Chemical group 0.000 claims abstract description 201
150000001875 compounds Chemical class 0.000 claims abstract description 160
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 107
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 100
239000001257 hydrogen Substances 0.000 claims abstract description 57
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 42
125000001424 substituent group Chemical group 0.000 claims abstract description 35
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 29
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 24
238000002360 preparation method Methods 0.000 claims abstract description 13
125000004185 ester group Chemical group 0.000 claims abstract description 7
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims abstract description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 201
-1 (lower)-alkanoyloxy Chemical group 0.000 claims description 122
238000000034 method Methods 0.000 claims description 104
239000002253 acid Substances 0.000 claims description 80
125000000623 heterocyclic group Chemical class 0.000 claims description 70
125000003282 alkyl amino group Chemical group 0.000 claims description 59
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 48
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 48
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 37
125000003545 alkoxy group Chemical group 0.000 claims description 34
229910052757 nitrogen Inorganic materials 0.000 claims description 24
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 21
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
125000001931 aliphatic group Chemical group 0.000 claims description 19
150000003254 radicals Chemical class 0.000 claims description 14
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 13
239000003795 chemical substances by application Substances 0.000 claims description 11
125000005236 alkanoylamino group Chemical group 0.000 claims description 10
150000002431 hydrogen Chemical group 0.000 claims description 10
125000004414 alkyl thio group Chemical group 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
125000004043 oxo group Chemical group O=* 0.000 claims description 8
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 7
239000012442 inert solvent Substances 0.000 claims description 6
125000003342 alkenyl group Chemical group 0.000 claims description 5
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
150000004820 halides Chemical class 0.000 claims description 5
229910052717 sulfur Inorganic materials 0.000 claims description 5
JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical group [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 4
150000008064 anhydrides Chemical class 0.000 claims description 4
229910004727 OSO3H Inorganic materials 0.000 claims description 3
125000001475 halogen functional group Chemical group 0.000 claims 6
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
229910006074 SO2NH2 Inorganic materials 0.000 claims 2
229910006069 SO3H Inorganic materials 0.000 claims 2
150000003839 salts Chemical class 0.000 abstract description 36
150000002961 penems Chemical class 0.000 abstract description 11
230000003389 potentiating effect Effects 0.000 abstract description 4
230000000844 anti-bacterial effect Effects 0.000 abstract description 2
VBQCHPIMZGQLAZ-UHFFFAOYSA-N phosphorane Chemical class [PH5] VBQCHPIMZGQLAZ-UHFFFAOYSA-N 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 421
239000000243 solution Substances 0.000 description 324
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 255
239000000203 mixture Substances 0.000 description 221
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 219
229910001868 water Inorganic materials 0.000 description 202
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 201
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 197
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 195
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 193
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 133
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 120
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 103
239000007787 solid Substances 0.000 description 99
239000012267 brine Substances 0.000 description 93
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 92
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 92
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 88
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 87
239000003921 oil Substances 0.000 description 75
235000019198 oils Nutrition 0.000 description 75
235000019439 ethyl acetate Nutrition 0.000 description 68
229910000030 sodium bicarbonate Inorganic materials 0.000 description 66
239000011541 reaction mixture Substances 0.000 description 65
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 63
GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical group C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 60
229940093499 ethyl acetate Drugs 0.000 description 59
QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 57
239000002904 solvent Substances 0.000 description 56
239000000741 silica gel Substances 0.000 description 55
229910002027 silica gel Inorganic materials 0.000 description 55
229960001866 silicon dioxide Drugs 0.000 description 55
150000002148 esters Chemical group 0.000 description 53
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 51
239000000047 product Substances 0.000 description 49
229910052943 magnesium sulfate Inorganic materials 0.000 description 46
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 46
238000006243 chemical reaction Methods 0.000 description 45
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 45
SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(I) nitrate Inorganic materials [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 43
235000017557 sodium bicarbonate Nutrition 0.000 description 43
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 42
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 40
239000000460 chlorine Substances 0.000 description 40
239000011734 sodium Substances 0.000 description 40
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 39
125000003118 aryl group Chemical group 0.000 description 38
238000001704 evaporation Methods 0.000 description 38
230000008020 evaporation Effects 0.000 description 38
229910052709 silver Inorganic materials 0.000 description 38
239000004332 silver Substances 0.000 description 38
239000000706 filtrate Substances 0.000 description 36
238000003756 stirring Methods 0.000 description 36
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 36
BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 35
239000002585 base Substances 0.000 description 33
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 32
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
239000010410 layer Substances 0.000 description 27
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 27
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 26
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
238000001914 filtration Methods 0.000 description 24
235000019341 magnesium sulphate Nutrition 0.000 description 24
238000010992 reflux Methods 0.000 description 24
239000007858 starting material Substances 0.000 description 24
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
229940086542 triethylamine Drugs 0.000 description 24
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 23
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
229910052708 sodium Inorganic materials 0.000 description 22
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 21
MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 21
229960001407 sodium bicarbonate Drugs 0.000 description 21
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 18
239000003610 charcoal Substances 0.000 description 18
239000000284 extract Substances 0.000 description 18
239000000377 silicon dioxide Substances 0.000 description 18
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 17
239000003054 catalyst Substances 0.000 description 17
238000005481 NMR spectroscopy Methods 0.000 description 16
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 16
WPUJEWVVTKLMQI-UHFFFAOYSA-N benzene;ethoxyethane Chemical compound CCOCC.C1=CC=CC=C1 WPUJEWVVTKLMQI-UHFFFAOYSA-N 0.000 description 16
229910052799 carbon Inorganic materials 0.000 description 16
238000004587 chromatography analysis Methods 0.000 description 16
239000012074 organic phase Substances 0.000 description 16
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
238000004440 column chromatography Methods 0.000 description 15
125000005843 halogen group Chemical group 0.000 description 15
238000000746 purification Methods 0.000 description 15
238000000935 solvent evaporation Methods 0.000 description 15
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 14
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
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 14
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
229940043279 diisopropylamine Drugs 0.000 description 14
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 13
239000012346 acetyl chloride Substances 0.000 description 13
WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 13
238000001816 cooling Methods 0.000 description 13
239000002808 molecular sieve Substances 0.000 description 13
239000012299 nitrogen atmosphere Substances 0.000 description 13
229910052763 palladium Inorganic materials 0.000 description 13
229910001961 silver nitrate Inorganic materials 0.000 description 13
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 13
229910052938 sodium sulfate Inorganic materials 0.000 description 13
235000011152 sodium sulphate Nutrition 0.000 description 13
239000000725 suspension Substances 0.000 description 13
229910052681 coesite Inorganic materials 0.000 description 12
229910052906 cristobalite Inorganic materials 0.000 description 12
239000003480 eluent Substances 0.000 description 12
239000006260 foam Substances 0.000 description 12
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 12
150000002500 ions Chemical class 0.000 description 12
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 12
239000002244 precipitate Substances 0.000 description 12
235000012239 silicon dioxide Nutrition 0.000 description 12
229910052682 stishovite Inorganic materials 0.000 description 12
229910052905 tridymite Inorganic materials 0.000 description 12
ZCTHWZKWCUEIHN-UHFFFAOYSA-N 4-tritylsulfanylazetidin-2-one Chemical compound N1C(=O)CC1SC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 ZCTHWZKWCUEIHN-UHFFFAOYSA-N 0.000 description 11
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 11
125000004432 carbon atom Chemical group C* 0.000 description 11
238000001035 drying Methods 0.000 description 11
HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 11
239000006188 syrup Substances 0.000 description 11
235000020357 syrup Nutrition 0.000 description 11
238000005406 washing Methods 0.000 description 11
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
235000019270 ammonium chloride Nutrition 0.000 description 10
239000007832 Na2SO4 Substances 0.000 description 9
230000010933 acylation Effects 0.000 description 9
238000005917 acylation reaction Methods 0.000 description 9
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
238000002425 crystallisation Methods 0.000 description 9
230000008025 crystallization Effects 0.000 description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
239000000463 material Substances 0.000 description 9
239000000843 powder Substances 0.000 description 9
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
150000001450 anions Chemical class 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 8
229910052744 lithium Inorganic materials 0.000 description 8
239000012071 phase Substances 0.000 description 8
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 7
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
239000008346 aqueous phase Substances 0.000 description 7
150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
239000012039 electrophile Substances 0.000 description 7
238000010828 elution Methods 0.000 description 7
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 7
239000003960 organic solvent Substances 0.000 description 7
239000011591 potassium Substances 0.000 description 7
229910052700 potassium Inorganic materials 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
159000000000 sodium salts Chemical class 0.000 description 7
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 7
MNVCCKVPSGWSCN-RXMQYKEDSA-N (5r)-3-methyl-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound S1C(C)=C(C(O)=O)N2C(=O)C[C@H]21 MNVCCKVPSGWSCN-RXMQYKEDSA-N 0.000 description 6
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 6
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
125000004423 acyloxy group Chemical group 0.000 description 6
150000001298 alcohols Chemical class 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 6
238000010348 incorporation Methods 0.000 description 6
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
HVRMNEPIBIGCNZ-UHFFFAOYSA-N (4-nitrophenyl)methyl 2-oxoacetate Chemical compound [O-][N+](=O)C1=CC=C(COC(=O)C=O)C=C1 HVRMNEPIBIGCNZ-UHFFFAOYSA-N 0.000 description 5
DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 5
DWDDFMFCVGDERN-UHFFFAOYSA-N 1-chloroazetidin-2-one Chemical compound ClN1CCC1=O DWDDFMFCVGDERN-UHFFFAOYSA-N 0.000 description 5
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239000011777 magnesium Substances 0.000 description 1
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238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
229940099990 ogen Drugs 0.000 description 1
239000004533 oil dispersion Substances 0.000 description 1
238000006053 organic reaction Methods 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229940049953 phenylacetate Drugs 0.000 description 1
NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
238000006303 photolysis reaction Methods 0.000 description 1
230000015843 photosynthesis, light reaction Effects 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
ZUFQCVZBBNZMKD-UHFFFAOYSA-M potassium 2-ethylhexanoate Chemical compound [K+].CCCCC(CC)C([O-])=O ZUFQCVZBBNZMKD-UHFFFAOYSA-M 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
238000004237 preparative chromatography Methods 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
229910052702 rhenium Inorganic materials 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
ZADZMOWCAUMICY-UHFFFAOYSA-N s-(2-oxoazetidin-1-yl) ethanethioate Chemical compound CC(=O)SN1CCC1=O ZADZMOWCAUMICY-UHFFFAOYSA-N 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
230000007017 scission Effects 0.000 description 1
150000003378 silver Chemical class 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
229910052979 sodium sulfide Inorganic materials 0.000 description 1
GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 1
VWMRHWQOUZWXNN-UHFFFAOYSA-M sodium;5-methyl-1,3-thiazole-4-carboxylate Chemical compound [Na+].CC=1SC=NC=1C([O-])=O VWMRHWQOUZWXNN-UHFFFAOYSA-M 0.000 description 1
XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical compound [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 1
239000008279 sol Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
238000007614 solvation Methods 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
QXKXDIKCIPXUPL-UHFFFAOYSA-N sulfanylidenemercury Chemical compound [Hg]=S QXKXDIKCIPXUPL-UHFFFAOYSA-N 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000011593 sulfur Chemical group 0.000 description 1
239000003826 tablet Substances 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000017105 transposition Effects 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
125000006000 trichloroethyl group Chemical group 0.000 description 1
RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 1
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
238000005866 tritylation reaction Methods 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
229920001567 vinyl ester resin Polymers 0.000 description 1
238000010792 warming Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1

CA423146 1978-12-18 1979-12-17 Intermediaires du phosphorane utilises dans la preparation de penems antibiotiques Expired CA1268183C (fr)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US968,663		1978-12-18

Publications (1)

Publication Number	Publication Date
CA1268183C true CA1268183C (fr)	1990-04-25

Publication	Publication Date	Title
GB2042515A (en)	1980-09-24	Antibacterial agents
EP0010316B1 (fr)	1983-10-05	Acides 1-carba-2-pénem-3-carboxyliques 1-, 6- et 2-substitués, procédé pour leur préparation et compositions pharmaceutiques les contenant
US4255330A (en)	1981-03-10	Process for preparing 6-substituted amino-2-substituted-pen-2-em-3-carboxylic acid
CA1221356A (fr)	1987-05-05	COMPOSES DE .beta.-LACTAM, PREPARATION ET UTILISATION
US4631150A (en)	1986-12-23	Process for the preparation of penems
JPH0314037B2 (fr)	1991-02-25
SE436130B (sv)	1984-11-12	Sett att framstella 1-karba-2-penem-3-karboxylsyror
US4262009A (en)	1981-04-14	6- And 1,1-disubstituted-1-carbadethiapen-2-em-3-carboxylic acid
US4218459A (en)	1980-08-19	6-Amido-1-carba-2-penem-3-carboxylic acid
CA1136617A (fr)	1982-11-30	Composes penem substitues en positions 2 et 6
CA1286661C (fr)	1991-07-23	Composes de type penem disubstitues en 2,6
US4267188A (en)	1981-05-12	5-Substituted-1-carba-pen-2-em-3-carboxylic acid
CA1268183C (fr)	1990-04-25	Intermediaires du phosphorane utilises dans la preparation de penems antibiotiques
CA1227194A (fr)	1987-09-22	Derives penem antibacteriens
US4600713A (en)	1986-07-15	1-, 6- and 2-substituted-1-carba-2-penem-3-carboxylic acids
US4684724A (en)	1987-08-04	4-Cyano-2-azetidinones and production thereof
JPS588085A (ja)	1983-01-18	光学活性トランス−６−置換−５（ｒ）−２−ペネム−３−カルボン酸誘導体の製造法及びこうして得られた化合物
US4374065A (en)	1983-02-15	Antibacterial agents of the β-lactam type
US4461727A (en)	1984-07-24	4-Acylthioazetidinone intermediates for antibacterial agents
IE50596B1 (en)	1986-05-28	Penem compounds
US4406834A (en)	1983-09-27	2,6 Disubstituted penems and intermediates therefor
EP0091755A1 (fr)	1983-10-19	Dérivés de pénicilline, un procédé pour leur préparation et compositions les contenant
JPH07109282A (ja)	1995-04-25	ヒドロキシシクロペンタノン誘導体及びその製造法
EP0187500A1 (fr)	1986-07-16	Monobactames
JPS61500495A (ja)	1986-03-20	複素環置換ペネム類

CA1268183C - Intermediaires du phosphorane utilises dans la preparation de penems antibiotiques - Google Patents

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