AU2005263655A1 - Process for preparing nitrooxy esters, nitrooxy thioesters, nitrooxy carbonates and nitrooxy thiocarbonates, intermediates useful in said process and preparation thereof - Google Patents
Process for preparing nitrooxy esters, nitrooxy thioesters, nitrooxy carbonates and nitrooxy thiocarbonates, intermediates useful in said process and preparation thereof Download PDFInfo
- Publication number
- AU2005263655A1 AU2005263655A1 AU2005263655A AU2005263655A AU2005263655A1 AU 2005263655 A1 AU2005263655 A1 AU 2005263655A1 AU 2005263655 A AU2005263655 A AU 2005263655A AU 2005263655 A AU2005263655 A AU 2005263655A AU 2005263655 A1 AU2005263655 A1 AU 2005263655A1
- Authority
- AU
- Australia
- Prior art keywords
- group
- nitrooxy
- formula
- integer
- pct
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims description 47
- -1 nitrooxy thioesters Chemical class 0.000 title claims description 24
- 125000001893 nitrooxy group Chemical group [O-][N+](=O)O* 0.000 title claims description 12
- 239000000543 intermediate Substances 0.000 title claims description 7
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title description 20
- GGWDZHYSPNNXIZ-UHFFFAOYSA-N nitrooxy hydrogen carbonate Chemical class OC(=O)OO[N+]([O-])=O GGWDZHYSPNNXIZ-UHFFFAOYSA-N 0.000 title description 2
- VDXDNALSAWYVJR-UHFFFAOYSA-N nitroperoxymethanethioic S-acid Chemical class C(=O)(OO[N+](=O)[O-])S VDXDNALSAWYVJR-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 89
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 claims description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 125000002947 alkylene group Chemical group 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- PNERJLFIGBYJAE-UHFFFAOYSA-N (2,3,4,5,6-pentafluorophenyl) 4-nitrooxybutanoate Chemical compound [O-][N+](=O)OCCCC(=O)OC1=C(F)C(F)=C(F)C(F)=C1F PNERJLFIGBYJAE-UHFFFAOYSA-N 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 8
- ZETOHPSSBWBMED-UHFFFAOYSA-N 4-nitrooxybutanoic acid Chemical compound OC(=O)CCCO[N+]([O-])=O ZETOHPSSBWBMED-UHFFFAOYSA-N 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- WZPWTXZSQHIABL-UHFFFAOYSA-N (2,3,4,5,6-pentafluorophenyl) benzoate Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1OC(=O)C1=CC=CC=C1 WZPWTXZSQHIABL-UHFFFAOYSA-N 0.000 claims description 4
- 239000002841 Lewis acid Substances 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 150000007517 lewis acids Chemical class 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- 239000001301 oxygen Chemical group 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- UPADJIXRYFZEMN-UHFFFAOYSA-N (2,3,4,5,6-pentafluorophenyl) 5-nitrooxypentanoate Chemical compound [O-][N+](=O)OCCCCC(=O)OC1=C(F)C(F)=C(F)C(F)=C1F UPADJIXRYFZEMN-UHFFFAOYSA-N 0.000 claims description 3
- QAEKLEXOVPBKLZ-UHFFFAOYSA-N 4-nitrooxybutyl (2,3,4,5,6-pentafluorophenyl) carbonate Chemical compound [O-][N+](=O)OCCCCOC(=O)OC1=C(F)C(F)=C(F)C(F)=C1F QAEKLEXOVPBKLZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000011593 sulfur Chemical group 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims 2
- 229910004679 ONO2 Inorganic materials 0.000 claims 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
- 230000015572 biosynthetic process Effects 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 25
- 238000003786 synthesis reaction Methods 0.000 description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 239000000203 mixture Substances 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- 101710134784 Agnoprotein Proteins 0.000 description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- PSIFNNKUMBGKDQ-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 PSIFNNKUMBGKDQ-UHFFFAOYSA-N 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
- GRHQDJDRGZFIPO-UHFFFAOYSA-N 4-bromobutanoic acid Chemical compound OC(=O)CCCBr GRHQDJDRGZFIPO-UHFFFAOYSA-N 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 7
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 229910052727 yttrium Inorganic materials 0.000 description 6
- XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 5
- 239000002083 C09CA01 - Losartan Substances 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229960004773 losartan Drugs 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 239000000010 aprotic solvent Substances 0.000 description 3
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 3
- 229960000830 captopril Drugs 0.000 description 3
- 239000011968 lewis acid catalyst Substances 0.000 description 3
- 125000001453 quaternary ammonium group Chemical group 0.000 description 3
- HZXJVDYQRYYYOR-UHFFFAOYSA-K scandium(iii) trifluoromethanesulfonate Chemical compound [Sc+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HZXJVDYQRYYYOR-UHFFFAOYSA-K 0.000 description 3
- 150000003536 tetrazoles Chemical group 0.000 description 3
- XDLJOYHUQWPLSN-UHFFFAOYSA-N (2,3,4,5,6-pentafluorophenyl) 4-(bromomethyl)benzoate Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1OC(=O)C1=CC=C(CBr)C=C1 XDLJOYHUQWPLSN-UHFFFAOYSA-N 0.000 description 2
- WBMIQBCBWZHXQZ-UHFFFAOYSA-N (2,3,4,5,6-pentafluorophenyl) 4-bromobutanoate Chemical compound FC1=C(F)C(F)=C(OC(=O)CCCBr)C(F)=C1F WBMIQBCBWZHXQZ-UHFFFAOYSA-N 0.000 description 2
- CBJDSWMAYMSPCL-UHFFFAOYSA-N (2,3,4,5,6-pentafluorophenyl) 5-bromopentanoate Chemical compound FC1=C(F)C(F)=C(OC(=O)CCCCBr)C(F)=C1F CBJDSWMAYMSPCL-UHFFFAOYSA-N 0.000 description 2
- XTMOQAKCOFLCRZ-UHFFFAOYSA-N (4-acetamidophenyl) 4-nitrooxybutanoate Chemical compound CC(=O)NC1=CC=C(OC(=O)CCCO[N+]([O-])=O)C=C1 XTMOQAKCOFLCRZ-UHFFFAOYSA-N 0.000 description 2
- KSEBMYQBYZTDHS-HWKANZROSA-M (E)-Ferulic acid Natural products COC1=CC(\C=C\C([O-])=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-M 0.000 description 2
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 2
- LVWOCJTWQFQXOM-UHFFFAOYSA-N 4-chlorobutyl (2,3,4,5,6-pentafluorophenyl) carbonate Chemical compound FC1=C(F)C(F)=C(OC(=O)OCCCCCl)C(F)=C1F LVWOCJTWQFQXOM-UHFFFAOYSA-N 0.000 description 2
- UXMFJNQGVKCJSG-UHFFFAOYSA-N 4-iodobutyl (2,3,4,5,6-pentafluorophenyl) carbonate Chemical compound FC1=C(F)C(F)=C(OC(=O)OCCCCI)C(F)=C1F UXMFJNQGVKCJSG-UHFFFAOYSA-N 0.000 description 2
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- FWBMAHHSOIGDKN-UHFFFAOYSA-N [3-(bromomethyl)phenyl] (4-nitrophenyl) carbonate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC(=O)OC1=CC=CC(CBr)=C1 FWBMAHHSOIGDKN-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 229960004436 budesonide Drugs 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
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
- 125000002843 carboxylic acid group Chemical group 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 229940114124 ferulic acid Drugs 0.000 description 2
- KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 description 2
- KSEBMYQBYZTDHS-UHFFFAOYSA-N ferulic acid Natural products COC1=CC(C=CC(O)=O)=CC=C1O KSEBMYQBYZTDHS-UHFFFAOYSA-N 0.000 description 2
- 235000001785 ferulic acid Nutrition 0.000 description 2
- 229960003469 flumetasone Drugs 0.000 description 2
- WXURHACBFYSXBI-GQKYHHCASA-N flumethasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]2(C)C[C@@H]1O WXURHACBFYSXBI-GQKYHHCASA-N 0.000 description 2
- 229960000676 flunisolide Drugs 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229960000890 hydrocortisone Drugs 0.000 description 2
- 230000000802 nitrating effect Effects 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 229960005205 prednisolone Drugs 0.000 description 2
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 2
- 229960002429 proline Drugs 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 229910001961 silver nitrate Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 150000003573 thiols Chemical group 0.000 description 2
- 229960004605 timolol Drugs 0.000 description 2
- QURCVMIEKCOAJU-UHFFFAOYSA-N trans-isoferulic acid Natural products COC1=CC=C(C=CC(O)=O)C=C1O QURCVMIEKCOAJU-UHFFFAOYSA-N 0.000 description 2
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 1
- JHQONOCFAYZOEQ-UHFFFAOYSA-N 3-(bromomethyl)phenol Chemical compound OC1=CC=CC(CBr)=C1 JHQONOCFAYZOEQ-UHFFFAOYSA-N 0.000 description 1
- CQQSQBRPAJSTFB-UHFFFAOYSA-N 4-(bromomethyl)benzoic acid Chemical compound OC(=O)C1=CC=C(CBr)C=C1 CQQSQBRPAJSTFB-UHFFFAOYSA-N 0.000 description 1
- OTDWRXBRYNVCDN-UHFFFAOYSA-N 4-chlorobutyl carbonochloridate Chemical compound ClCCCCOC(Cl)=O OTDWRXBRYNVCDN-UHFFFAOYSA-N 0.000 description 1
- LGCBVEQNSDSLIH-UHFFFAOYSA-N 4-pyridin-3-ylbutanal Chemical compound O=CCCCC1=CC=CN=C1 LGCBVEQNSDSLIH-UHFFFAOYSA-N 0.000 description 1
- WNXNUPJZWYOKMW-UHFFFAOYSA-N 5-bromopentanoic acid Chemical compound OC(=O)CCCCBr WNXNUPJZWYOKMW-UHFFFAOYSA-N 0.000 description 1
- MLVOHHYLVXZIBW-UHFFFAOYSA-N 5-nitrooxypentanoic acid Chemical compound OC(=O)CCCCO[N+]([O-])=O MLVOHHYLVXZIBW-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- WHXDLJOHWHFXJR-UHFFFAOYSA-N CC(=O)NC1=CC=C(O)C=C1.CC(=O)NC1=CC=C(O)C=C1 Chemical compound CC(=O)NC1=CC=C(O)C=C1.CC(=O)NC1=CC=C(O)C=C1 WHXDLJOHWHFXJR-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Chemical group 0.000 description 1
- ZEFHZKHMFWTXMB-UHFFFAOYSA-N [2-butyl-5-chloro-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methyl 4-nitrooxybutanoate Chemical compound CCCCC1=NC(Cl)=C(COC(=O)CCCO[N+]([O-])=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 ZEFHZKHMFWTXMB-UHFFFAOYSA-N 0.000 description 1
- CCALZSTUWJROFY-UHFFFAOYSA-N [2-butyl-5-chloro-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methyl 5-nitrooxypentanoate Chemical compound CCCCC1=NC(Cl)=C(COC(=O)CCCCO[N+]([O-])=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 CCALZSTUWJROFY-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 125000001743 benzylic group Chemical group 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 125000002993 cycloalkylene group Chemical group 0.000 description 1
- 125000004956 cyclohexylene group Chemical group 0.000 description 1
- 125000004979 cyclopentylene group Chemical group 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910001960 metal nitrate Inorganic materials 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 150000004714 phosphonium salts Chemical group 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/02—Preparation of esters of nitric acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C203/00—Esters of nitric or nitrous acid
- C07C203/02—Esters of nitric acid
- C07C203/04—Esters of nitric acid having nitrate groups bound to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C203/00—Esters of nitric or nitrous acid
- C07C203/02—Esters of nitric acid
- C07C203/10—Esters of nitric acid having nitrate groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- 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
- C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
- C07D207/10—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 no double bonds between ring members or between ring members and non-ring members 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
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/06—1,2,3-Thiadiazoles; Hydrogenated 1,2,3-thiadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/10—1,2,5-Thiadiazoles; Hydrogenated 1,2,5-thiadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AUPCT/EP2004/051550 | 2004-07-20 | ||
| PCT/EP2004/051550 WO2005011646A2 (en) | 2003-07-31 | 2004-07-20 | Nitrooxy derivatives of losartan, valsatan, candesartan, telmisartan, eprosartan and olmesartan as angiotensin-ii receptor blockers for the treatment of cardiovascular diseases |
| PCT/EP2005/050459 WO2006008196A1 (en) | 2004-07-20 | 2005-02-02 | Process for preparing nitrooxy esters, nitrooxy thioesters, nitrooxy carbonates and nitrooxy thiocarbonates, intermediates useful in said process and preparation thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2005263655A1 true AU2005263655A1 (en) | 2006-01-26 |
Family
ID=34960502
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2005263655A Abandoned AU2005263655A1 (en) | 2004-07-20 | 2005-02-02 | Process for preparing nitrooxy esters, nitrooxy thioesters, nitrooxy carbonates and nitrooxy thiocarbonates, intermediates useful in said process and preparation thereof |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7723529B2 (enExample) |
| EP (1) | EP1778617A1 (enExample) |
| JP (1) | JP2008506748A (enExample) |
| CN (1) | CN1984871A (enExample) |
| AU (1) | AU2005263655A1 (enExample) |
| CA (1) | CA2574666A1 (enExample) |
| WO (1) | WO2006008196A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008074450A2 (en) * | 2006-12-20 | 2008-06-26 | Nicox S.A. | Non-peptidic renin inhibitors nitroderivatives |
| US20110052674A1 (en) * | 2008-02-26 | 2011-03-03 | Merck Sharp & Dohme Corp. | Angiotensin ii receptor blocker derivatives |
| EP2250158A2 (en) * | 2008-02-26 | 2010-11-17 | Nicox S.A. | Angiotensin ii receptor antagonists |
| CN102498088A (zh) * | 2009-09-15 | 2012-06-13 | 帝斯曼知识产权资产管理有限公司 | 硝基氧基酯及其制备和用途 |
| WO2011092065A1 (en) | 2010-01-29 | 2011-08-04 | Nicox S.A. | Nitric oxide releasing compounds for the treatment of neurophatic pain |
| WO2011101245A1 (en) | 2010-02-18 | 2011-08-25 | Nicox S.A. | Nitric oxide releasing compounds for the treatment of neuropathic pain |
| US9871201B2 (en) * | 2012-03-15 | 2018-01-16 | Merck Patent Gmbh | Electronic devices |
| WO2021195126A1 (en) | 2020-03-24 | 2021-09-30 | Burnet Michael W | Anti-infective and anti-viral compounds and compositions |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4105776A (en) | 1976-06-21 | 1978-08-08 | E. R. Squibb & Sons, Inc. | Proline derivatives and related compounds |
| US4046889A (en) | 1976-02-13 | 1977-09-06 | E. R. Squibb & Sons, Inc. | Azetidine-2-carboxylic acid derivatives |
| JPS60181083A (ja) * | 1984-02-29 | 1985-09-14 | Kowa Co | 新規ラセミ体及びその変換方法 |
| IT1314184B1 (it) * | 1999-08-12 | 2002-12-06 | Nicox Sa | Composizioni farmaceutiche per la terapia di condizioni di stressossidativo |
| US6696592B2 (en) | 2001-05-22 | 2004-02-24 | Nicox-S.A. | Methods of making 21-[4′-(nitrooxyalkyl)benzoate] corticosteroid derivatives and intermediates useful in the synthesis thereof |
| KR20060056352A (ko) | 2003-07-31 | 2006-05-24 | 니콕스 에스. 에이. | 안지오텐신ⅱ 수용체 차단제 유도체들 |
| WO2005054175A2 (en) * | 2003-11-20 | 2005-06-16 | Nicox S.A. | New process for the preparation of nitrooxyderivatives of paracetamol |
-
2005
- 2005-02-02 EP EP05707928A patent/EP1778617A1/en not_active Withdrawn
- 2005-02-02 WO PCT/EP2005/050459 patent/WO2006008196A1/en not_active Ceased
- 2005-02-02 AU AU2005263655A patent/AU2005263655A1/en not_active Abandoned
- 2005-02-02 JP JP2007521923A patent/JP2008506748A/ja not_active Withdrawn
- 2005-02-02 CA CA002574666A patent/CA2574666A1/en not_active Abandoned
- 2005-02-02 CN CNA2005800240517A patent/CN1984871A/zh active Pending
- 2005-02-02 US US11/632,666 patent/US7723529B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1984871A (zh) | 2007-06-20 |
| US7723529B2 (en) | 2010-05-25 |
| WO2006008196A1 (en) | 2006-01-26 |
| US20070238882A1 (en) | 2007-10-11 |
| JP2008506748A (ja) | 2008-03-06 |
| CA2574666A1 (en) | 2006-01-26 |
| EP1778617A1 (en) | 2007-05-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK1987048T3 (en) | Methods for the convergent synthesis of calicheamicin derivatives | |
| WO2017108960A1 (en) | Method for producing monomethyl fumarate compounds | |
| CA3030551A1 (en) | Processes for the preparation of 4-alkoxy-3-(acyl or alkyl)oxypicolinamides | |
| AU2005263655A1 (en) | Process for preparing nitrooxy esters, nitrooxy thioesters, nitrooxy carbonates and nitrooxy thiocarbonates, intermediates useful in said process and preparation thereof | |
| SK69695A3 (en) | Process for preparing benzofuran compounds | |
| JP7136527B2 (ja) | ３－［（３ｓ）－７－ブロモ－２－オキソ－５－（ピリジン－２－イル）－２，３－ジヒドロ－１ｈ－［１，４］－ベンゾジアゼピン－３－イル］プロピオン酸メチルエステルの調製方法及びその方法に有用な化合物 | |
| ES2251292A1 (es) | Procedimiento para la obtencion de un compuesto farmaceuticamente activo y de sus intermedios de sintesis. | |
| JP7163439B2 (ja) | カリケアマイシン誘導体を合成するための中間体および方法 | |
| WO2006079610A1 (en) | Nitrooxy sartan derivatives as angiotensin ii receptor blockers for the treatment of cardiovascular and inflammatory diseases | |
| JP7380555B2 (ja) | 重合性化合物の製造方法 | |
| HK1107807A (en) | Process for preparing nitrooxy esters, nitrooxy thioesters, nitrooxy carbonates and nitrooxy thiocarbonates, intermediates useful in said process and preparation thereof | |
| ES2288376B1 (es) | Procedimiento para la obtencion de intermedios utiles en la obtencion de un compuesto farmaceuticamente activo. | |
| CN111100063B (zh) | 一种合成2-氟甲基取代的吡咯烷、哌啶以及哌嗪衍生物的制备方法 | |
| JP2004018480A (ja) | ５−置換−１，２，４−トリアゾール−３−カルボン酸エステル誘導体の製造方法 | |
| HK1219721B (zh) | 用於合成加利车霉素衍生物的中间体和方法 | |
| BR112016009663B1 (pt) | Intermediários e métodos para a sintetização de derivados de caliqueamicina | |
| JP2004504378A (ja) | ジスタマイシン誘導体の合成方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |