DE69808093T2 - Verfahren zur herstellung von 2-substituierten 1-(tetrazol-5-yl)benzenverbindungen durch ortho-metallierung - Google Patents
Verfahren zur herstellung von 2-substituierten 1-(tetrazol-5-yl)benzenverbindungen durch ortho-metallierungInfo
- Publication number
- DE69808093T2 DE69808093T2 DE69808093T DE69808093T DE69808093T2 DE 69808093 T2 DE69808093 T2 DE 69808093T2 DE 69808093 T DE69808093 T DE 69808093T DE 69808093 T DE69808093 T DE 69808093T DE 69808093 T2 DE69808093 T2 DE 69808093T2
- Authority
- DE
- Germany
- Prior art keywords
- compound
- formula
- process according
- mmol
- compounds
- 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.)
- Expired - Lifetime
Links
- -1 2-SUBSTITUTED 1- (TETRAZOL-5-YL) Benzenes Chemical class 0.000 title claims description 19
- 238000004519 manufacturing process Methods 0.000 title 1
- 238000001465 metallisation Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims abstract description 38
- 238000006263 metalation reaction Methods 0.000 claims abstract description 15
- RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidine Chemical group CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 claims description 24
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical group CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 15
- 238000007122 ortho-metalation reaction Methods 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 8
- 230000003197 catalytic effect Effects 0.000 claims description 6
- 229940043279 diisopropylamine Drugs 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical group [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000011630 iodine Substances 0.000 claims description 4
- 150000003335 secondary amines Chemical class 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- 239000002081 C09CA05 - Tasosartan Substances 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 229960000651 tasosartan Drugs 0.000 claims description 3
- ADXGNEYLLLSOAR-UHFFFAOYSA-N tasosartan Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 ADXGNEYLLLSOAR-UHFFFAOYSA-N 0.000 claims description 3
- FMRWQLAJBBKXDM-UHFFFAOYSA-N 2,2,5,5-tetramethylpyrrolidine Chemical group CC1(C)CCC(C)(C)N1 FMRWQLAJBBKXDM-UHFFFAOYSA-N 0.000 claims description 2
- ZWXQPERWRDHCMZ-UHFFFAOYSA-N 2-methyl-n-propan-2-ylpropan-2-amine Chemical group CC(C)NC(C)(C)C ZWXQPERWRDHCMZ-UHFFFAOYSA-N 0.000 claims description 2
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical group C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 claims description 2
- 150000001408 amides Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 2
- OBYVIBDTOCAXSN-UHFFFAOYSA-N n-butan-2-ylbutan-2-amine Chemical group CCC(C)NC(C)CC OBYVIBDTOCAXSN-UHFFFAOYSA-N 0.000 claims description 2
- FUUUBHCENZGYJA-UHFFFAOYSA-N n-cyclopentylcyclopentanamine Chemical group C1CCCC1NC1CCCC1 FUUUBHCENZGYJA-UHFFFAOYSA-N 0.000 claims description 2
- CATWEXRJGNBIJD-UHFFFAOYSA-N n-tert-butyl-2-methylpropan-2-amine Chemical group CC(C)(C)NC(C)(C)C CATWEXRJGNBIJD-UHFFFAOYSA-N 0.000 claims description 2
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 2
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims 4
- MARUHZGHZWCEQU-UHFFFAOYSA-N 5-phenyl-2h-tetrazole Chemical class C1=CC=CC=C1C1=NNN=N1 MARUHZGHZWCEQU-UHFFFAOYSA-N 0.000 abstract description 11
- 229940123413 Angiotensin II antagonist Drugs 0.000 abstract description 8
- 239000002333 angiotensin II receptor antagonist Substances 0.000 abstract description 8
- 239000000543 intermediate Substances 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 239000000203 mixture Substances 0.000 description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 239000000725 suspension Substances 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000010992 reflux Methods 0.000 description 11
- VYDLZOWMGPAVLN-UHFFFAOYSA-N 5-(2-methyl-1-phenylpropan-2-yl)-2h-tetrazole Chemical compound N1=NNN=C1C(C)(C)CC1=CC=CC=C1 VYDLZOWMGPAVLN-UHFFFAOYSA-N 0.000 description 10
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 9
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 7
- 238000006880 cross-coupling reaction Methods 0.000 description 6
- 239000011701 zinc Substances 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 229910052749 magnesium Inorganic materials 0.000 description 5
- 238000006478 transmetalation reaction Methods 0.000 description 5
- 229910052725 zinc Inorganic materials 0.000 description 5
- 235000005074 zinc chloride Nutrition 0.000 description 5
- 239000011592 zinc chloride Substances 0.000 description 5
- RIGIQZIXVFCURM-UHFFFAOYSA-N 8-[(4-bromophenyl)methyl]-2,4-dimethyl-5,6-dihydropyrido[2,3-d]pyrimidin-7-one Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC1=CC=C(Br)C=C1 RIGIQZIXVFCURM-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 150000002900 organolithium compounds Chemical class 0.000 description 4
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- OBTZDIRUQWFRFZ-UHFFFAOYSA-N 2-(5-methylfuran-2-yl)-n-(4-methylphenyl)quinoline-4-carboxamide Chemical compound O1C(C)=CC=C1C1=CC(C(=O)NC=2C=CC(C)=CC=2)=C(C=CC=C2)C2=N1 OBTZDIRUQWFRFZ-UHFFFAOYSA-N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 150000004791 alkyl magnesium halides Chemical class 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000006138 lithiation reaction Methods 0.000 description 2
- 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 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- CMSMSYXAJAPWOS-UHFFFAOYSA-N 5-phenyl-2h-tetrazole;sodium Chemical compound [Na].C1=CC=CC=C1C1=NNN=N1 CMSMSYXAJAPWOS-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- NICRXUZBFPUWQZ-UHFFFAOYSA-N C(C)(C)(C)C1=C(C=CC=C1)[Mg]C1=NN=NN1 Chemical compound C(C)(C)(C)C1=C(C=CC=C1)[Mg]C1=NN=NN1 NICRXUZBFPUWQZ-UHFFFAOYSA-N 0.000 description 1
- 239000002083 C09CA01 - Losartan Substances 0.000 description 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
- 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 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 description 1
- 229960000932 candesartan Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 150000002641 lithium Chemical class 0.000 description 1
- 229960004773 losartan Drugs 0.000 description 1
- CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 description 1
- SCEZYJKGDJPHQO-UHFFFAOYSA-M magnesium;methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=CC=C1 SCEZYJKGDJPHQO-UHFFFAOYSA-M 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- 150000002780 morpholines Chemical class 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 150000008048 phenylpyrazoles Chemical class 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000000758 substrate Substances 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
- 150000003536 tetrazoles Chemical group 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 229960004699 valsartan Drugs 0.000 description 1
- ACWBQPMHZXGDFX-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=NN1 ACWBQPMHZXGDFX-QFIPXVFZSA-N 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/02—Magnesium compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT97MI001544A IT1292437B1 (it) | 1997-06-30 | 1997-06-30 | Processo di orto-metallazione utile per la sintesi di 1 - tetrazol- 5-il) benzeni 2-sostituiti |
| PCT/EP1998/003969 WO1999001459A1 (en) | 1997-06-30 | 1998-06-29 | Ortho-metalation process for the synthesis of 2-substituted-1-(tetrazol-5-yl)benzenes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69808093D1 DE69808093D1 (de) | 2002-10-24 |
| DE69808093T2 true DE69808093T2 (de) | 2003-06-05 |
Family
ID=11377464
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69808093T Expired - Lifetime DE69808093T2 (de) | 1997-06-30 | 1998-06-29 | Verfahren zur herstellung von 2-substituierten 1-(tetrazol-5-yl)benzenverbindungen durch ortho-metallierung |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6271375B1 (enExample) |
| EP (1) | EP0994881B1 (enExample) |
| JP (1) | JP4128633B2 (enExample) |
| AT (1) | ATE224395T1 (enExample) |
| CA (1) | CA2294609C (enExample) |
| CZ (1) | CZ293277B6 (enExample) |
| DE (1) | DE69808093T2 (enExample) |
| ES (1) | ES2182349T3 (enExample) |
| HU (1) | HU226471B1 (enExample) |
| IL (1) | IL133249A (enExample) |
| IT (1) | IT1292437B1 (enExample) |
| WO (1) | WO1999001459A1 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2371554C (en) * | 1999-04-28 | 2009-06-09 | Shizue Nakagawa | Pharmaceutical composition comprising an angiotensin ii antagonist for preventing, treating or development-inhibiting simple retinopathy and preproliferative retinopathy |
| JP4405388B2 (ja) | 2002-07-26 | 2010-01-27 | エイ・エム・オー・フローニンゲン・ベー・ベー | 眼内レンズの操作方法および装置 |
| CN1759113A (zh) * | 2003-01-16 | 2006-04-12 | 特瓦制药工业有限公司 | 伊贝沙坦的新合成方法 |
| US7199144B2 (en) | 2003-04-21 | 2007-04-03 | Teva Pharmaceuticals Industries, Ltd. | Process for the preparation of valsartan and intermediates thereof |
| EP1950204A1 (en) | 2003-03-17 | 2008-07-30 | Teva Pharmaceutical Industries Ltd. | Amorphous form of valsartan |
| DE602004013405T2 (de) * | 2003-03-17 | 2009-05-07 | Teva Pharmaceutical Industries Ltd. | Polymorphe formen von valsartan |
| EP1618097A1 (en) * | 2003-04-21 | 2006-01-25 | Teva Pharmaceutical Industries Ltd | Process for the preparation of valsartan |
| WO2004094391A2 (en) * | 2003-04-21 | 2004-11-04 | Teva Pharmaceutical Industries Ltd. | Process for the preparation of valsartan and intermediates thereof |
| PL1660463T3 (pl) | 2003-08-08 | 2008-05-30 | Dipharma Francis Srl | Sposób wytwarzania pochodnych fenylotetrazolu |
| WO2005049587A1 (en) * | 2003-11-21 | 2005-06-02 | Ranbaxy Laboratories Limited | Process for preparation of biphenyl tetrazole |
| WO2005118166A2 (en) | 2004-06-04 | 2005-12-15 | Teva Pharmaceutical Industries, Ltd. | Pharmaceutical composition containing irbesartan |
| ES2308591T3 (es) * | 2004-12-22 | 2008-12-01 | Algry Quimica, S.L | Intermedios para la preparacion de antagonistas de los receptores de la angiotensina ii. |
| US20090124577A1 (en) | 2004-12-22 | 2009-05-14 | Enantia Si | Intermediate Compounds for the Preparation of an Angiotensin II Receptor Antagonist |
| WO2007005967A2 (en) * | 2005-07-05 | 2007-01-11 | Teva Pharmaceutical Industries Ltd. | Process for preparing valsartan |
| US20090304797A1 (en) * | 2006-06-23 | 2009-12-10 | Tarur Venkatasubramanian Radha | Process for the Preparation of Micronized Valsartan |
| EP2090567A3 (en) | 2008-02-13 | 2011-06-01 | Ranbaxy Laboratories Limited | Processes for the preparation of intermediates of valsartan |
| WO2009125416A2 (en) * | 2008-04-07 | 2009-10-15 | Hetero Research Foundation | Process for preparation of valsartan intermediate |
| WO2012056294A1 (en) | 2010-10-29 | 2012-05-03 | Jubilant Life Sciences Ltd. | An improved process for the preparation of n-pentanoyl-n-[[2'-(1h-tetrazol-5-yi)[1,1'-biphenyl]-4-yi]methyl]-l-valine |
| WO2018002673A1 (en) | 2016-07-01 | 2018-01-04 | N4 Pharma Uk Limited | Novel formulations of angiotensin ii receptor antagonists |
| PL4037679T3 (pl) | 2019-12-02 | 2026-03-09 | Harman Finochem Limited | Sposób wytwarzania walsartanu o wysokiej czystości |
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| US5039814A (en) | 1990-05-02 | 1991-08-13 | Merck & Co., Inc. | Ortho-lithiation process for the synthesis of 2-substituted 1-(tetrazol-5-yl)benzenes |
| US5256654A (en) | 1991-10-24 | 1993-10-26 | American Home Products Corporation | Substituted pyrrolopyrimidines, azepinopyrimidines and pyridopyrimidines useful as angiotensin II antagonists |
| US5149699A (en) | 1991-10-24 | 1992-09-22 | American Home Products Corporation | Substituted pyridopyrimidines useful as antgiotensin II antagonists |
| TW226375B (enExample) * | 1991-10-24 | 1994-07-11 | American Home Prod | |
| EP0550313A1 (fr) | 1991-12-30 | 1993-07-07 | Synthelabo | Nouveaux dérivés de 2-(tétrazol-5-yl)-(1,1'-biphényle), leur préparation et leur utilisation comme intermédiaires de synthèse |
| US5310929A (en) * | 1992-08-06 | 1994-05-10 | E. I. Du Pont De Nemours And Company | Prodrugs of imidazole carboxylic acids as angiotensin II receptor antagonists |
| FR2696746B1 (fr) | 1992-10-12 | 1994-11-18 | Synthelabo | Dérivés de l'acide benzèneborinique, leur préparation et leur utilisation comme intermédiaires de synthèse. |
| EP0846117B1 (en) * | 1995-06-07 | 2003-05-14 | Wyeth | Process for preparation of biphenyl derivatives |
| US5760220A (en) | 1995-06-07 | 1998-06-02 | American Home Products Corporation | Process for preparation of biphenyl derivatives |
-
1997
- 1997-06-30 IT IT97MI001544A patent/IT1292437B1/it active IP Right Grant
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- 1998-06-29 WO PCT/EP1998/003969 patent/WO1999001459A1/en not_active Ceased
- 1998-06-29 IL IL13324998A patent/IL133249A/xx not_active IP Right Cessation
- 1998-06-29 US US09/445,470 patent/US6271375B1/en not_active Expired - Fee Related
- 1998-06-29 EP EP98936398A patent/EP0994881B1/en not_active Expired - Lifetime
- 1998-06-29 HU HU0004227A patent/HU226471B1/hu not_active IP Right Cessation
- 1998-06-29 DE DE69808093T patent/DE69808093T2/de not_active Expired - Lifetime
- 1998-06-29 JP JP50630899A patent/JP4128633B2/ja not_active Expired - Fee Related
- 1998-06-29 CA CA002294609A patent/CA2294609C/en not_active Expired - Fee Related
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- 1998-06-29 AT AT98936398T patent/ATE224395T1/de active
Also Published As
| Publication number | Publication date |
|---|---|
| IL133249A0 (en) | 2001-04-30 |
| ES2182349T3 (es) | 2003-03-01 |
| HUP0004227A3 (en) | 2003-03-28 |
| EP0994881A1 (en) | 2000-04-26 |
| ITMI971544A0 (enExample) | 1997-06-30 |
| HU226471B1 (en) | 2008-12-29 |
| CZ293277B6 (cs) | 2004-03-17 |
| CA2294609C (en) | 2008-08-19 |
| IT1292437B1 (it) | 1999-02-08 |
| HUP0004227A2 (hu) | 2001-06-28 |
| JP4128633B2 (ja) | 2008-07-30 |
| WO1999001459A1 (en) | 1999-01-14 |
| CZ477499A3 (cs) | 2000-07-12 |
| US6271375B1 (en) | 2001-08-07 |
| ITMI971544A1 (it) | 1998-12-30 |
| ATE224395T1 (de) | 2002-10-15 |
| EP0994881B1 (en) | 2002-09-18 |
| JP2002510314A (ja) | 2002-04-02 |
| IL133249A (en) | 2003-12-10 |
| DE69808093D1 (de) | 2002-10-24 |
| CA2294609A1 (en) | 1999-01-14 |
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Owner name: ZACH SYSTEM S.P.A., BRESSO, (MILANO), IT |