DE2528664A1 - Pyrrolidone und verfahren zu ihrer herstellung - Google Patents
Pyrrolidone und verfahren zu ihrer herstellungInfo
- Publication number
- DE2528664A1 DE2528664A1 DE19752528664 DE2528664A DE2528664A1 DE 2528664 A1 DE2528664 A1 DE 2528664A1 DE 19752528664 DE19752528664 DE 19752528664 DE 2528664 A DE2528664 A DE 2528664A DE 2528664 A1 DE2528664 A1 DE 2528664A1
- Authority
- DE
- Germany
- Prior art keywords
- formula
- compound
- pyrrolidone
- compounds
- meaning given
- Prior art date
- 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- Withdrawn
Links
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 title claims description 55
- 238000000034 method Methods 0.000 title claims description 25
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- -1 aliphatic Hydrocarbon radical Chemical class 0.000 claims description 275
- 150000001875 compounds Chemical class 0.000 claims description 208
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 67
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 54
- 239000002253 acid Substances 0.000 claims description 53
- 125000004432 carbon atom Chemical group C* 0.000 claims description 48
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 43
- 125000006239 protecting group Chemical group 0.000 claims description 41
- 239000002585 base Substances 0.000 claims description 33
- 150000002148 esters Chemical class 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 27
- 150000001450 anions Chemical class 0.000 claims description 25
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 23
- 229910052751 metal Inorganic materials 0.000 claims description 14
- 239000002184 metal Substances 0.000 claims description 14
- 230000002378 acidificating effect Effects 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 13
- 150000007513 acids Chemical class 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 230000032050 esterification Effects 0.000 claims description 8
- 238000005886 esterification reaction Methods 0.000 claims description 8
- 229930195733 hydrocarbon Natural products 0.000 claims description 8
- 238000005949 ozonolysis reaction Methods 0.000 claims description 8
- KHUXNRRPPZOJPT-UHFFFAOYSA-N phenoxy radical Chemical compound O=C1C=C[CH]C=C1 KHUXNRRPPZOJPT-UHFFFAOYSA-N 0.000 claims description 8
- 239000004215 Carbon black (E152) Substances 0.000 claims description 7
- 125000006241 alcohol protecting group Chemical group 0.000 claims description 7
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 7
- 229910052783 alkali metal Inorganic materials 0.000 claims description 6
- 150000004040 pyrrolidinones Chemical class 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000003158 alcohol group Chemical group 0.000 claims description 5
- 150000001340 alkali metals Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 230000002829 reductive effect Effects 0.000 claims description 5
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 150000003254 radicals Chemical class 0.000 claims description 4
- 125000005297 thienyloxy group Chemical group S1C(=CC=C1)O* 0.000 claims description 4
- 125000001931 aliphatic group Chemical group 0.000 claims description 3
- 238000003776 cleavage reaction Methods 0.000 claims description 3
- 230000007017 scission Effects 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 229940126601 medicinal product Drugs 0.000 claims description 2
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims description 2
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 239000012059 conventional drug carrier Substances 0.000 claims 1
- AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 96
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- 238000004587 chromatography analysis Methods 0.000 description 55
- 238000006243 chemical reaction Methods 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- 239000002904 solvent Substances 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 238000005804 alkylation reaction Methods 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- 230000029936 alkylation Effects 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 239000000203 mixture Substances 0.000 description 15
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 15
- 229960000583 acetic acid Drugs 0.000 description 13
- 230000003647 oxidation Effects 0.000 description 13
- 238000007254 oxidation reaction Methods 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000012362 glacial acetic acid Substances 0.000 description 12
- 125000003118 aryl group Chemical group 0.000 description 11
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
- 239000007795 chemical reaction product Substances 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 9
- 150000002170 ethers Chemical class 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 150000002576 ketones Chemical class 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 150000003180 prostaglandins Chemical class 0.000 description 7
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 150000001298 alcohols Chemical class 0.000 description 6
- 230000033228 biological regulation Effects 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 6
- LQZCYXCHWNQBKX-UHFFFAOYSA-N 1-dimethoxyphosphorylheptan-2-one Chemical compound CCCCCC(=O)CP(=O)(OC)OC LQZCYXCHWNQBKX-UHFFFAOYSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- OEWJGOMAYLEAKO-HYXAFXHYSA-N methyl (z)-7-bromohept-5-enoate Chemical compound COC(=O)CCC\C=C/CBr OEWJGOMAYLEAKO-HYXAFXHYSA-N 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 238000004140 cleaning Methods 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- GJFVJZNQGLSMMQ-RQOWECAXSA-N (z)-7-bromohept-5-enoic acid Chemical compound OC(=O)CCC\C=C/CBr GJFVJZNQGLSMMQ-RQOWECAXSA-N 0.000 description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 238000006052 Horner reaction Methods 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 238000007239 Wittig reaction Methods 0.000 description 3
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000011097 chromatography purification Methods 0.000 description 3
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
- 150000002084 enol ethers Chemical class 0.000 description 3
- 150000008282 halocarbons Chemical class 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 229960004592 isopropanol Drugs 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 235000006408 oxalic acid Nutrition 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000004611 spectroscopical analysis Methods 0.000 description 3
- 238000005292 vacuum distillation Methods 0.000 description 3
- PJEXUIKBGBSHBS-UHFFFAOYSA-N 1-(hydroxymethyl)pyrrolidin-2-one Chemical compound OCN1CCCC1=O PJEXUIKBGBSHBS-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 2
- HOBJEFOCIRXQKH-UHFFFAOYSA-N 5-(hydroxymethyl)pyrrolidin-2-one Chemical compound OCC1CCC(=O)N1 HOBJEFOCIRXQKH-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
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- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
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- FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 description 2
- PYBYLIYKZRCVBI-XQRVVYSFSA-N ethyl (z)-7-bromohept-5-enoate Chemical compound CCOC(=O)CCC\C=C/CBr PYBYLIYKZRCVBI-XQRVVYSFSA-N 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
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- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
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- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 125000000468 ketone group Chemical group 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- ARLQDYZAXIPMJQ-ARJAWSKDSA-N methyl (z)-hept-5-enoate Chemical compound COC(=O)CCC\C=C/C ARLQDYZAXIPMJQ-ARJAWSKDSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
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- 150000007530 organic bases Chemical class 0.000 description 2
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- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
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- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
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- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
Priority Applications (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752528664 DE2528664A1 (de) | 1975-06-27 | 1975-06-27 | Pyrrolidone und verfahren zu ihrer herstellung |
| NL7606773A NL7606773A (nl) | 1975-06-27 | 1976-06-22 | Werkwijze voor het bereiden van pyrrolidonen. |
| ES449095A ES449095A1 (es) | 1975-06-27 | 1976-06-22 | Procedimiento para la preparacion de pirrolidonas. |
| SE7607331A SE7607331L (sv) | 1975-06-27 | 1976-06-24 | Pyrrolidoner och forfarande for deras framstellning |
| CH809976A CH623809A5 (en) | 1975-06-27 | 1976-06-24 | Process for the preparation of pyrrolidones |
| LU75235A LU75235A1 (enrdf_load_stackoverflow) | 1975-06-27 | 1976-06-24 | |
| AT0467976A AT365575B (de) | 1975-06-27 | 1976-06-25 | Verfahren zur herstellung von neuen pyrrolidonen sowie deren physiologisch vertraeglichen metall- oder aminsalzen |
| CA255,666A CA1085859A (en) | 1975-06-27 | 1976-06-25 | Pyrrolidones and process for their manufacture |
| IL49916A IL49916A0 (en) | 1975-06-27 | 1976-06-25 | Pyrrolidones and process for their manufacture |
| GB26564/76A GB1553595A (en) | 1975-06-27 | 1976-06-25 | Pyrrolidones and process for their manufacture |
| DK287476A DK287476A (da) | 1975-06-27 | 1976-06-25 | Pyrrolidoner samt deres fremstilling og anvendelse |
| ZA763802A ZA763802B (en) | 1975-06-27 | 1976-06-25 | Pyrrolidones and process for their manufacture |
| JP51075954A JPS525764A (en) | 1975-06-27 | 1976-06-26 | Production of pyrrolidone |
| FR7619563A FR2316943A1 (fr) | 1975-06-27 | 1976-06-28 | Pyrrolidones et medicaments qui en contiennent |
| BE168390A BE843505A (fr) | 1975-06-27 | 1976-06-28 | Pyrrolidones et medicaments qui en contiennent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752528664 DE2528664A1 (de) | 1975-06-27 | 1975-06-27 | Pyrrolidone und verfahren zu ihrer herstellung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2528664A1 true DE2528664A1 (de) | 1977-01-13 |
Family
ID=5950059
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19752528664 Withdrawn DE2528664A1 (de) | 1975-06-27 | 1975-06-27 | Pyrrolidone und verfahren zu ihrer herstellung |
Country Status (14)
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0325984A3 (en) * | 1988-01-25 | 1991-01-02 | Hoechst-Roussel Pharmaceuticals Incorporated | 5-substituted 1-/4-(1-pyrrolidinyl)-2-butynyl/-2-pyrrolidones and related compounds, a process for their preparation and their use as medicaments |
| EP1110949A1 (en) * | 1999-12-22 | 2001-06-27 | Pfizer Products Inc. | EP4 receptor selective agonists in the treatment of osteoporosis |
| WO2003097596A1 (en) * | 2002-05-14 | 2003-11-27 | Allergan, Inc. | 8-azaprostaglandin analogs as agents for lowering intraocular pressure |
| WO2014144610A1 (en) * | 2013-03-15 | 2014-09-18 | Cayman Chemical Company, Inc. | Lactam compounds as ep4 receptor-selective agonists for use in the treatment of ep4-mediated diseases and conditions |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1077948A (en) * | 1976-08-06 | 1980-05-20 | Albin J. Nelson | 1,-5 disubstituted-2-pyrrolidones and processes for their production |
| WO2002024647A1 (fr) * | 2000-09-21 | 2002-03-28 | Ono Pharmaceutical Co., Ltd. | Agonistes du recepteur de l'ep4 comprenant comme principe actif des derives de la 8-azaprostaglandine |
| EE200300246A (et) | 2000-11-27 | 2003-10-15 | Pfizer Products Inc. | EP4 retseptori suhtes selektiivsed agonistid osteoporoosi raviks |
| PT1408961E (pt) | 2001-07-16 | 2007-10-10 | Ono Pharmaceutical Co | Derivados de 2-pirrolidona como agonistas de prostanóides |
| ATE315022T1 (de) | 2001-07-16 | 2006-02-15 | Hoffmann La Roche | Prostaglandinanaloga als ep4-rezeptoragonisten |
| RU2303451C2 (ru) | 2001-07-23 | 2007-07-27 | Оно Фармасьютикал Ко., Лтд. | Фармацевтические композиции для лечения заболеваний, связанных с уменьшением костной массы, включающие агонист ер4 в качестве активного ингредиента |
| ATE336247T1 (de) * | 2002-03-18 | 2006-09-15 | Pfizer Prod Inc | Verwendung von selektiven ep4 rezeptor agonisten zur behandlung von krankheiten |
| CA2511255C (en) | 2003-01-10 | 2009-04-07 | F. Hoffmann-La Roche Ag | 2-piperidone derivatives as prostaglandin agonists |
| US7179820B2 (en) | 2003-06-06 | 2007-02-20 | Allergan, Inc. | Piperidinyl prostaglandin E analogs |
| SI2875022T1 (sl) | 2012-07-19 | 2017-04-26 | Cayman Chemical Company, Incorporated | Spojine difluorolaktama kot selektivni antagonisti EP4 za uporabo pri zdravljenju z EP4-povzročenih bolezni in stanj |
| WO2014144584A2 (en) | 2013-03-15 | 2014-09-18 | Cayman Chemical Company, Inc. | Lactam compounds as ep4 receptor-selective agonists for use in the treatment of ep4-mediated diseases and conditions |
| CA2903314C (en) | 2013-03-15 | 2023-02-14 | Cayman Chemical Company, Inc. | Methods of synthesizing a difluorolactam analog |
| US10729810B2 (en) | 2013-07-19 | 2020-08-04 | Cayman Chemical Company, Inc | Methods, systems, and compositions for promoting bone growth |
-
1975
- 1975-06-27 DE DE19752528664 patent/DE2528664A1/de not_active Withdrawn
-
1976
- 1976-06-22 NL NL7606773A patent/NL7606773A/xx not_active Application Discontinuation
- 1976-06-22 ES ES449095A patent/ES449095A1/es not_active Expired
- 1976-06-24 SE SE7607331A patent/SE7607331L/xx unknown
- 1976-06-24 CH CH809976A patent/CH623809A5/de not_active IP Right Cessation
- 1976-06-24 LU LU75235A patent/LU75235A1/xx unknown
- 1976-06-25 IL IL49916A patent/IL49916A0/xx unknown
- 1976-06-25 DK DK287476A patent/DK287476A/da unknown
- 1976-06-25 AT AT0467976A patent/AT365575B/de active
- 1976-06-25 ZA ZA763802A patent/ZA763802B/xx unknown
- 1976-06-25 GB GB26564/76A patent/GB1553595A/en not_active Expired
- 1976-06-26 JP JP51075954A patent/JPS525764A/ja active Pending
- 1976-06-28 FR FR7619563A patent/FR2316943A1/fr active Granted
- 1976-06-28 BE BE168390A patent/BE843505A/xx not_active IP Right Cessation
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0325984A3 (en) * | 1988-01-25 | 1991-01-02 | Hoechst-Roussel Pharmaceuticals Incorporated | 5-substituted 1-/4-(1-pyrrolidinyl)-2-butynyl/-2-pyrrolidones and related compounds, a process for their preparation and their use as medicaments |
| EP1110949A1 (en) * | 1999-12-22 | 2001-06-27 | Pfizer Products Inc. | EP4 receptor selective agonists in the treatment of osteoporosis |
| WO2001046140A1 (en) * | 1999-12-22 | 2001-06-28 | Pfizer Products Inc. | Ep4 receptor selective agonists in the treatment of osteoporosis |
| US6642266B2 (en) | 1999-12-22 | 2003-11-04 | Pfizer Inc. | EP4 receptor selective agonists in the treatment of osteoporosis |
| WO2003097596A1 (en) * | 2002-05-14 | 2003-11-27 | Allergan, Inc. | 8-azaprostaglandin analogs as agents for lowering intraocular pressure |
| US6906097B2 (en) | 2002-05-14 | 2005-06-14 | Allergan, Inc. | 8-azaprostaglandin analogs as agents for lowering intraocular pressure |
| CN1313447C (zh) * | 2002-05-14 | 2007-05-02 | 阿勒根公司 | 用于降低眼内压的8－氮杂前列腺素类似物 |
| WO2014144610A1 (en) * | 2013-03-15 | 2014-09-18 | Cayman Chemical Company, Inc. | Lactam compounds as ep4 receptor-selective agonists for use in the treatment of ep4-mediated diseases and conditions |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS525764A (en) | 1977-01-17 |
| ES449095A1 (es) | 1977-12-16 |
| ATA467976A (de) | 1981-06-15 |
| CH623809A5 (en) | 1981-06-30 |
| LU75235A1 (enrdf_load_stackoverflow) | 1977-03-16 |
| ZA763802B (en) | 1977-05-25 |
| DK287476A (da) | 1976-12-28 |
| NL7606773A (nl) | 1976-12-29 |
| FR2316943A1 (fr) | 1977-02-04 |
| GB1553595A (en) | 1979-09-26 |
| FR2316943B1 (enrdf_load_stackoverflow) | 1978-11-03 |
| SE7607331L (sv) | 1976-12-28 |
| IL49916A0 (en) | 1976-08-31 |
| BE843505A (fr) | 1976-12-28 |
| AT365575B (de) | 1982-01-25 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8110 | Request for examination paragraph 44 | ||
| 8130 | Withdrawal |