WO1997001564A1 - Improved process for synthesizing carbapenem intermediates - Google Patents
Improved process for synthesizing carbapenem intermediates Download PDFInfo
- Publication number
- WO1997001564A1 WO1997001564A1 PCT/US1996/010783 US9610783W WO9701564A1 WO 1997001564 A1 WO1997001564 A1 WO 1997001564A1 US 9610783 W US9610783 W US 9610783W WO 9701564 A1 WO9701564 A1 WO 9701564A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound
- formula
- substantially non
- base
- reactive solvent
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 29
- 230000008569 process Effects 0.000 title claims abstract description 23
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 11
- 239000000543 intermediate Substances 0.000 title description 18
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 title description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 37
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 15
- -1 triethylsilyl Chemical group 0.000 claims abstract description 8
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 29
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 claims description 9
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 8
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 7
- 229940011051 isopropyl acetate Drugs 0.000 claims description 6
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims 4
- 239000000243 solution Substances 0.000 description 13
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 0 C[C@]([C@@]([C@@]([C@@](*)C(C(C(*)=O)=N)=O)N1)C1=O)O Chemical compound C[C@]([C@@]([C@@]([C@@](*)C(C(C(*)=O)=N)=O)N1)C1=O)O 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000003242 anti bacterial agent Substances 0.000 description 5
- 229940088710 antibiotic agent Drugs 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000008363 phosphate buffer Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 229940041011 carbapenems Drugs 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 4
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- HDKCVDHYIIKWFM-UHFFFAOYSA-K octanoate;rhodium(3+) Chemical compound [Rh+3].CCCCCCCC([O-])=O.CCCCCCCC([O-])=O.CCCCCCCC([O-])=O HDKCVDHYIIKWFM-UHFFFAOYSA-K 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 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 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 150000008049 diazo compounds Chemical class 0.000 description 2
- ASMQGLCHMVWBQR-UHFFFAOYSA-M diphenyl phosphate Chemical compound C=1C=CC=CC=1OP(=O)([O-])OC1=CC=CC=C1 ASMQGLCHMVWBQR-UHFFFAOYSA-M 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- UQSQSQZYBQSBJZ-UHFFFAOYSA-M fluorosulfonate Chemical compound [O-]S(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-M 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- QAPTWHXHEYAIKG-RCOXNQKVSA-N n-[(1r,2s,5r)-5-(tert-butylamino)-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 QAPTWHXHEYAIKG-RCOXNQKVSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 2
- 229940102001 zinc bromide Drugs 0.000 description 2
- QKLXBIHSGMPUQS-FGZHOGPDSA-M (3r,5r)-7-[4-(4-fluorophenyl)-2,5-dimethyl-1-phenylpyrrol-3-yl]-3,5-dihydroxyheptanoate Chemical compound CC1=C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C(C)N1C1=CC=CC=C1 QKLXBIHSGMPUQS-FGZHOGPDSA-M 0.000 description 1
- YKMONJZIUAOVEM-WDSKDSINSA-N 1beta-methylcarbapenem Chemical compound C[C@H]1C=CN2C(=O)C[C@@H]12 YKMONJZIUAOVEM-WDSKDSINSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical group [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical compound C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical group 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical group I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- MKDJIADBNUOBJH-UHFFFAOYSA-N octanoic acid;rhodium Chemical compound [Rh].[Rh].CCCCCCCC(O)=O.CCCCCCCC(O)=O.CCCCCCCC(O)=O.CCCCCCCC(O)=O MKDJIADBNUOBJH-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- CDXVUROVRIFQMV-UHFFFAOYSA-N oxo(diphenoxy)phosphanium Chemical compound C=1C=CC=CC=1O[P+](=O)OC1=CC=CC=C1 CDXVUROVRIFQMV-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical compound [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- JQKHNBQZGUKYPX-UHFFFAOYSA-N tris(2,4,6-trimethoxyphenyl)phosphane Chemical compound COC1=CC(OC)=CC(OC)=C1P(C=1C(=CC(OC)=CC=1OC)OC)C1=C(OC)C=C(OC)C=C1OC JQKHNBQZGUKYPX-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D477/00—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring
- C07D477/02—Preparation
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/188—Preparation; Treatments not provided for in C07F7/20 by reactions involving the formation of Si-O linkages
Definitions
- the present invention is related to an improved synthesis of carbapenem intermediates, and in particular, the following compounds:
- the present invention overcomes these disadvantages, providing a scheme which avoids unstable intermediates, and in many instances, producing intermediates which are in crystalline form, requiring little or no purification before futher use.
- R represents H or methyl and P represents triethylsilyl or trimethylsilyl.
- the process comprises treating a compound of the formula:
- the 1 - ⁇ methyl isomer of the final product is more resistant to deactivation than the IH or the 1- ⁇ methyl isomer.
- the bicyclic ketoester 2 can be further reacted at the 2- position to establish a leaving group, e.g., L, which represents diphenyl phosphate, triflate, tosylate, mesylate, fluorosulfonate, chloride and the like, to form the appropriate activated carbapenem intermediate.
- the activated carbapenem intermediate is suitable for coupling to a substituent at position 2, for example, through the use of a palladium catalyst, e.g., Pd2(dba)3*CHCl3, and tris(2, 4, 6- trimethoxyphenyl)phosphine in a suitable solvent. Further details regarding coupling reactions can be obtained from U.S. Patent No. 5,034,384.
- a compound of formula 3 wherein R represents H or methyl is reacted with P-Cl in the presence of base and a substantially non-reactive solvent to produce a compound of formula 1 :
- a compound of formula 3 is reacted with P-Cl wherein P represents triethylsilyl to produce a compound of formula la:
- a compound of formula 3 is reacted with P-Cl wherein P represents trimethylsilyl to produce a compound of formula lb:
- a compound of formula 4 wherein R represents H or methyl is reacted with P-Cl in the presence of base and a substantially non-reactive solvent to produce a compound of formula 2:
- a compound of formula 4 is reacted with P-Cl wherein P represents triethylsilyl to produce a compound of formula 2a:
- a compound of formula 4 is reacted with P-Cl wherein P represents trimethylsilyl to produce a compound of formula 2b:
- the substituted azetidinone is cyclized before protection of the hydroxyethyl side chain. After cyclization, the side chain is protected with P.
- PNB refers to the protecting group para- nitrobenzyl.
- THF tetrahydrofuran
- OAc refers to acetate, CH3C(0)0-.
- EtOAc solvent ethyl acetate
- iPrOAc isopropyl acetate
- TES refers to the group triethylsilyl.
- TMS refers to the group trimethylsilyl.
- Et3N refers to triethylamine.
- dba refers to dibenzylideneacetone.
- the objects of the present invention are to utilize crystalline intermediates and to avoid unstable intermediates. Additionally, stereospecificity and regiospecific reactions are favored. The following schemes are representative.
- the anhydride L2O or the halide L-Cl can be combined with the bicyclic ketoester in the presence of a nitrogen containing base and in a substantially non-reactive solvent to produce the activated carbapenem 5.
- the activated carbapenem 5, with the appropriate group L at position 2 can then be coupled to an appropriate substituent according to the procedures set forth in U. S. Pat. No. 5,034,384.
- Carbapenems which can be synthesized in accordance with the process described herein are disclosed, and the groups which are appropriate for such attachment, can be found, e.g., in U.S. Pat. No. 5,034,384.
- the preferred substantially non-reactive solvents used herein are dimethylformamide, tetrahydrofuran (THF), isopropyl acetate, ethyl acetate and methylene chloride. Most preferably, mixtures thereof are used.
- the preferred base used in the processes described herein is imidazole.
- the nitrogen containing bases for use in the activating reaction with L2O or L-Cl include triethylamine, diisopropylethylamine and diisopropylamine.
- L examples include the sulfonate leaving groups, such as trifluoromethanesulfonate (triflate), methanesulfonate (mesylate), toluenesulfonate (tosylate) and fluorosulfonate, the phosphonic acid residues, such as diphenylphosphonate and the halide leaving groups, such as chloride, bromide or iodide.
- triflate OTf
- OSO2F flurorosulfonate
- OMs mesylate
- the batch was aged at 20 °C for 2 hr.
- the reaction mixture was assayed by HPLC.
- the starting material should be less than 0.15 area % at 245 nm.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Priority Applications (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9903016A HUP9903016A3 (en) | 1995-06-28 | 1996-06-24 | Improved process for synthesizing carbapenem intermediates |
| EA199800096A EA199800096A1 (ru) | 1995-06-28 | 1996-06-24 | Способ получения промежуточных продуктов для синтеза карбапенема |
| AU63921/96A AU696543B2 (en) | 1995-06-28 | 1996-06-24 | Improved process for synthesizing carbapenem intermediates |
| EP96923404A EP0836607A1 (en) | 1995-06-28 | 1996-06-24 | Improved process for synthesizing carbapenem intermediates |
| JP9504502A JPH11513979A (ja) | 1995-06-28 | 1996-06-24 | カルバペネム中間体を合成するための改良されたプロセス |
| BR9609338A BR9609338A (pt) | 1995-06-28 | 1996-06-24 | Processo para sintetizar um composto |
| SK1765-97A SK176597A3 (en) | 1995-06-28 | 1996-06-24 | Improved process for synthesizing carbapenem intermediates |
| MXPA/A/1998/000041A MXPA98000041A (en) | 1995-06-28 | 1998-01-07 | Improved procedure to synthetic carbape intermediaries |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US58595P | 1995-06-28 | 1995-06-28 | |
| US60/000,585 | 1995-06-28 | ||
| GBGB9602921.0A GB9602921D0 (en) | 1996-02-13 | 1996-02-13 | Improved process for synthesizing carbapenem intermediates |
| GB9602921.0 | 1996-02-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1997001564A1 true WO1997001564A1 (en) | 1997-01-16 |
Family
ID=26308678
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1996/010783 WO1997001564A1 (en) | 1995-06-28 | 1996-06-24 | Improved process for synthesizing carbapenem intermediates |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP0836607A1 (hu) |
| JP (1) | JPH11513979A (hu) |
| KR (1) | KR19990028406A (hu) |
| CN (1) | CN1193322A (hu) |
| AR (1) | AR002507A1 (hu) |
| AU (1) | AU696543B2 (hu) |
| BR (1) | BR9609338A (hu) |
| CA (1) | CA2224439A1 (hu) |
| CZ (1) | CZ419097A3 (hu) |
| EA (1) | EA199800096A1 (hu) |
| HU (1) | HUP9903016A3 (hu) |
| SK (1) | SK176597A3 (hu) |
| WO (1) | WO1997001564A1 (hu) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2009277936B2 (en) | 2008-07-30 | 2014-11-27 | Sun Pharmaceutical Industries Limited | Process for the preparation of carbapenem compounds |
| WO2011048583A1 (en) | 2009-10-23 | 2011-04-28 | Ranbaxy Laboratories Limited | Process for the preparation of carbapenem compounds |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2165247A (en) * | 1984-10-02 | 1986-04-09 | Bristol Myers Co | Azabicycloheptene derivatives |
| EP0409331A2 (en) * | 1989-07-18 | 1991-01-23 | Merck & Co. Inc. | A novel process for the preparation of 2-diazo-3-trisubstituted silyloxy-3-butenoates |
| EP0414904A1 (en) * | 1989-01-12 | 1991-03-06 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Preparation of enol silyl ether compounds |
| EP0422472A2 (de) * | 1989-10-12 | 1991-04-17 | Bayer Ag | Verfahren zur Herstellung von O-silylierten Hydroxylverbindungen und ihre Verwendung zur Herstellung von Estergruppen aufweisenden Isocyanaten |
-
1996
- 1996-06-18 AR ARP960103190A patent/AR002507A1/es unknown
- 1996-06-24 JP JP9504502A patent/JPH11513979A/ja active Pending
- 1996-06-24 CN CN96196325A patent/CN1193322A/zh active Pending
- 1996-06-24 CZ CZ974190A patent/CZ419097A3/cs unknown
- 1996-06-24 KR KR1019970709722A patent/KR19990028406A/ko not_active Application Discontinuation
- 1996-06-24 CA CA002224439A patent/CA2224439A1/en not_active Abandoned
- 1996-06-24 SK SK1765-97A patent/SK176597A3/sk unknown
- 1996-06-24 EA EA199800096A patent/EA199800096A1/ru unknown
- 1996-06-24 EP EP96923404A patent/EP0836607A1/en not_active Withdrawn
- 1996-06-24 AU AU63921/96A patent/AU696543B2/en not_active Ceased
- 1996-06-24 HU HU9903016A patent/HUP9903016A3/hu unknown
- 1996-06-24 BR BR9609338A patent/BR9609338A/pt unknown
- 1996-06-24 WO PCT/US1996/010783 patent/WO1997001564A1/en not_active Application Discontinuation
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2165247A (en) * | 1984-10-02 | 1986-04-09 | Bristol Myers Co | Azabicycloheptene derivatives |
| EP0414904A1 (en) * | 1989-01-12 | 1991-03-06 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Preparation of enol silyl ether compounds |
| EP0409331A2 (en) * | 1989-07-18 | 1991-01-23 | Merck & Co. Inc. | A novel process for the preparation of 2-diazo-3-trisubstituted silyloxy-3-butenoates |
| EP0422472A2 (de) * | 1989-10-12 | 1991-04-17 | Bayer Ag | Verfahren zur Herstellung von O-silylierten Hydroxylverbindungen und ihre Verwendung zur Herstellung von Estergruppen aufweisenden Isocyanaten |
Also Published As
| Publication number | Publication date |
|---|---|
| AR002507A1 (es) | 1998-03-25 |
| CZ419097A3 (cs) | 1998-07-15 |
| HUP9903016A3 (en) | 2000-04-28 |
| MX9800041A (es) | 1998-08-30 |
| AU6392196A (en) | 1997-01-30 |
| BR9609338A (pt) | 1999-05-11 |
| KR19990028406A (ko) | 1999-04-15 |
| SK176597A3 (en) | 1998-07-08 |
| EA199800096A1 (ru) | 1998-08-27 |
| CA2224439A1 (en) | 1997-01-16 |
| EP0836607A1 (en) | 1998-04-22 |
| AU696543B2 (en) | 1998-09-10 |
| HUP9903016A2 (hu) | 2000-03-28 |
| CN1193322A (zh) | 1998-09-16 |
| JPH11513979A (ja) | 1999-11-30 |
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