FI112945B - Tetratsolyylifenyyliboorihappovälituotteita AII-reseptoriantagonistien synteesiä varten - Google Patents

Tetratsolyylifenyyliboorihappovälituotteita AII-reseptoriantagonistien synteesiä varten Download PDF

Info

Publication number: FI112945B
Authority: FI; Finland
Prior art keywords: palladium; triphenylmethyl; process according; bis; carbonate
Prior art date: 1991-11-18

Application number

FI942282A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI942282A0 (fi

FI942282A (fi

Inventor

Young Sek Lo

Lucius Thomas Rossano

Robert D Larsen

Anthony O King

Original Assignee

Du Pont

Merck & Co Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1991-11-18

Filing date

1994-05-17

Publication date

2004-02-13

1991-11-18 Priority claimed from US07/793,514 external-priority patent/US5130439A/en

1992-07-10 Priority claimed from US07/911,812 external-priority patent/US5310928A/en

1992-07-10 Priority claimed from US07/911,813 external-priority patent/US5206374A/en

1994-05-17 Application filed by Du Pont, Merck & Co Inc filed Critical Du Pont

1994-05-17 Publication of FI942282A0 publication Critical patent/FI942282A0/fi

1994-05-17 Publication of FI942282A publication Critical patent/FI942282A/fi

2004-02-13 Application granted granted Critical

2004-02-13 Publication of FI112945B publication Critical patent/FI112945B/fi

Links

239000002253 acid Substances 0.000 title abstract description 20
239000000543 intermediate Substances 0.000 title abstract description 5
239000002464 receptor antagonist Substances 0.000 title description 7
229940044551 receptor antagonist Drugs 0.000 title description 7
230000015572 biosynthetic process Effects 0.000 title description 5
238000003786 synthesis reaction Methods 0.000 title description 3
238000000034 method Methods 0.000 claims abstract description 64
-1 biphenyl tetrazole compound Chemical class 0.000 claims abstract description 36
150000001875 compounds Chemical class 0.000 claims abstract description 32
238000002360 preparation method Methods 0.000 claims abstract description 15
229910052700 potassium Inorganic materials 0.000 claims abstract description 6
239000011591 potassium Substances 0.000 claims abstract description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 84
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 80
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 79
239000000203 mixture Substances 0.000 claims description 58
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 42
230000008569 process Effects 0.000 claims description 42
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 42
238000006243 chemical reaction Methods 0.000 claims description 33
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 31
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 28
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 26
239000002904 solvent Substances 0.000 claims description 26
229910052757 nitrogen Inorganic materials 0.000 claims description 24
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 24
239000011541 reaction mixture Substances 0.000 claims description 23
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 17
239000003054 catalyst Substances 0.000 claims description 16
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
KLKFAASOGCDTDT-UHFFFAOYSA-N ethoxymethoxyethane Chemical compound CCOCOCC KLKFAASOGCDTDT-UHFFFAOYSA-N 0.000 claims description 15
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 14
229910000027 potassium carbonate Inorganic materials 0.000 claims description 14
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 14
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 13
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 11
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical group CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 11
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 11
125000000217 alkyl group Chemical group 0.000 claims description 11
229910052763 palladium Inorganic materials 0.000 claims description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 10
239000003960 organic solvent Substances 0.000 claims description 9
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 8
238000005859 coupling reaction Methods 0.000 claims description 8
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 8
239000000460 chlorine Substances 0.000 claims description 7
229910052801 chlorine Inorganic materials 0.000 claims description 7
230000008878 coupling Effects 0.000 claims description 7
238000010168 coupling process Methods 0.000 claims description 7
239000012039 electrophile Substances 0.000 claims description 7
229910052751 metal Inorganic materials 0.000 claims description 7
239000002184 metal Substances 0.000 claims description 7
INIOZDBICVTGEO-UHFFFAOYSA-L palladium(ii) bromide Chemical compound Br[Pd]Br INIOZDBICVTGEO-UHFFFAOYSA-L 0.000 claims description 7
SJHCUXCOGGKFAI-UHFFFAOYSA-N tripropan-2-yl phosphite Chemical compound CC(C)OP(OC(C)C)OC(C)C SJHCUXCOGGKFAI-UHFFFAOYSA-N 0.000 claims description 7
BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 claims description 6
WTZGPCBXPZNQIU-UHFFFAOYSA-L benzyl(trimethyl)azanium;carbonate Chemical compound [O-]C([O-])=O.C[N+](C)(C)CC1=CC=CC=C1.C[N+](C)(C)CC1=CC=CC=C1 WTZGPCBXPZNQIU-UHFFFAOYSA-L 0.000 claims description 6
229910052794 bromium Inorganic materials 0.000 claims description 6
125000001309 chloro group Chemical group Cl* 0.000 claims description 6
125000004849 alkoxymethyl group Chemical group 0.000 claims description 5
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
150000007529 inorganic bases Chemical class 0.000 claims description 5
238000000746 purification Methods 0.000 claims description 5
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 5
CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 claims description 4
QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 claims description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 4
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 4
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 4
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 4
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
239000001099 ammonium carbonate Substances 0.000 claims description 4
235000012501 ammonium carbonate Nutrition 0.000 claims description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 claims description 4
229910052744 lithium Inorganic materials 0.000 claims description 4
230000000269 nucleophilic effect Effects 0.000 claims description 4
QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 claims description 4
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
229960005235 piperonyl butoxide Drugs 0.000 claims description 4
125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 claims description 4
229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
229910021515 thallium hydroxide Inorganic materials 0.000 claims description 4
QGYXCSSUHCHXHB-UHFFFAOYSA-M thallium(i) hydroxide Chemical compound [OH-].[Tl+] QGYXCSSUHCHXHB-UHFFFAOYSA-M 0.000 claims description 4
TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 3
NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 claims description 3
125000001246 bromo group Chemical group Br* 0.000 claims description 3
HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 claims description 3
125000005842 heteroatom Chemical group 0.000 claims description 3
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 claims description 3
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 3
229910052708 sodium Inorganic materials 0.000 claims description 3
239000011734 sodium Substances 0.000 claims description 3
DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical group CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 claims description 3
UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 claims description 2
IBXMKLPFLZYRQZ-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 IBXMKLPFLZYRQZ-UHFFFAOYSA-N 0.000 claims description 2
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 claims description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
239000000010 aprotic solvent Substances 0.000 claims description 2
239000012298 atmosphere Substances 0.000 claims description 2
FHKVBKRABWGIMY-UHFFFAOYSA-M benzyl(trimethyl)azanium;methyl carbonate Chemical compound COC([O-])=O.C[N+](C)(C)CC1=CC=CC=C1 FHKVBKRABWGIMY-UHFFFAOYSA-M 0.000 claims description 2
150000001639 boron compounds Chemical class 0.000 claims description 2
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
229910052731 fluorine Inorganic materials 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical class 0.000 claims description 2
239000001257 hydrogen Substances 0.000 claims description 2
229910052739 hydrogen Inorganic materials 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
239000011777 magnesium Substances 0.000 claims description 2
229910052749 magnesium Inorganic materials 0.000 claims description 2
229910052759 nickel Inorganic materials 0.000 claims description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 claims description 2
125000005010 perfluoroalkyl group Chemical group 0.000 claims description 2
KHUXNRRPPZOJPT-UHFFFAOYSA-N phenoxy radical Chemical group O=C1C=C[CH]C=C1 KHUXNRRPPZOJPT-UHFFFAOYSA-N 0.000 claims description 2
125000001424 substituent group Chemical group 0.000 claims description 2
229910052717 sulfur Inorganic materials 0.000 claims description 2
239000011593 sulfur Chemical group 0.000 claims description 2
VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 claims description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
125000004122 cyclic group Chemical group 0.000 claims 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 2
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims 2
125000003944 tolyl group Chemical group 0.000 claims 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
101100203596 Caenorhabditis elegans sol-1 gene Proteins 0.000 claims 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
SMTUJUHULKBTBS-UHFFFAOYSA-N benzyl(trimethyl)azanium;methanolate Chemical compound [O-]C.C[N+](C)(C)CC1=CC=CC=C1 SMTUJUHULKBTBS-UHFFFAOYSA-N 0.000 claims 1
GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 claims 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
239000001301 oxygen Chemical group 0.000 claims 1
229910052760 oxygen Chemical group 0.000 claims 1
229910000073 phosphorus hydride Inorganic materials 0.000 claims 1
229910052697 platinum Inorganic materials 0.000 claims 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
150000007513 acids Chemical class 0.000 abstract description 6
239000002333 angiotensin II receptor antagonist Substances 0.000 abstract description 3
239000000243 solution Substances 0.000 description 48
239000007787 solid Substances 0.000 description 28
RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 24
239000000047 product Substances 0.000 description 23
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 22
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
239000000725 suspension Substances 0.000 description 21
238000001914 filtration Methods 0.000 description 19
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
238000003756 stirring Methods 0.000 description 18
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
239000012065 filter cake Substances 0.000 description 14
239000000706 filtrate Substances 0.000 description 14
239000012044 organic layer Substances 0.000 description 13
239000012299 nitrogen atmosphere Substances 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
239000010410 layer Substances 0.000 description 9
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
238000010926 purge Methods 0.000 description 8
238000010992 reflux Methods 0.000 description 8
239000012279 sodium borohydride Substances 0.000 description 7
229910000033 sodium borohydride Inorganic materials 0.000 description 7
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
238000004821 distillation Methods 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000007864 aqueous solution Substances 0.000 description 5
239000003921 oil Substances 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
150000003536 tetrazoles Chemical class 0.000 description 5
JLVIHQCWASNXCK-UHFFFAOYSA-N 2-butyl-5-chloro-1h-imidazole-4-carbaldehyde Chemical compound CCCCC1=NC(C=O)=C(Cl)N1 JLVIHQCWASNXCK-UHFFFAOYSA-N 0.000 description 4
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Classifications

- 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
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/05—Cyclic compounds having at least one ring containing boron but no carbon in the ring
- 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
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Plural Heterocyclic Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

FI942282A 1991-11-18 1994-05-17 Tetratsolyylifenyyliboorihappovälituotteita AII-reseptoriantagonistien synteesiä varten FI112945B (fi)

Applications Claiming Priority (8)

Application Number	Priority Date	Filing Date	Title
US79351491		1991-11-18
US07/793,514 US5130439A (en)	1991-11-18	1991-11-18	Tetrazolylphenylboronic acid intermediates for the synthesis of AII receptor antagonists
US07/911,812 US5310928A (en)	1991-11-18	1992-07-10	Process for preparing biphenyltetrazole compounds
US07/911,813 US5206374A (en)	1991-11-18	1992-07-10	Process for preparing tetrazolylphenylboronic acid intermediates
US91181292		1992-07-10
US91181392		1992-07-10
PCT/US1992/009979 WO1993010106A1 (en)	1991-11-18	1992-11-18	Tetrazolylphenylboronic acid intermediates for the synthesis of aii receptor antagonists
US9209979		1992-11-18

Publications (3)

Publication Number	Publication Date
FI942282A0 FI942282A0 (fi)	1994-05-17
FI942282A FI942282A (fi)	1994-05-17
FI112945B true FI112945B (fi)	2004-02-13

Family

ID=27419904

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI942282A FI112945B (fi)	1991-11-18	1994-05-17	Tetratsolyylifenyyliboorihappovälituotteita AII-reseptoriantagonistien synteesiä varten

Country Status (14)

Country	Link
EP (2)	EP0643704B1 (de)
JP (1)	JPH08500323A (de)
KR (2)	KR100212257B1 (de)
AT (2)	ATE395341T1 (de)
AU (1)	AU665388B2 (de)
CA (1)	CA2123900C (de)
CZ (1)	CZ283954B6 (de)
DE (2)	DE69233208T2 (de)
DK (1)	DK0643704T3 (de)
ES (1)	ES2203614T3 (de)
FI (1)	FI112945B (de)
NO (1)	NO307932B1 (de)
SK (1)	SK280887B6 (de)
WO (1)	WO1993010106A1 (de)

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DE4319041A1 (de) *	1992-10-23	1994-04-28	Bayer Ag	Trisubstituierte Biphenyle
WO1996009301A1 (fr) *	1994-09-20	1996-03-28	Wakunaga Seiyaku Kabushiki Kaisha	Procede de production d'un derive de n-biphenylmethylthiadiazoline ou un sel de celui-ci et son intermediaire de production
ATE214388T1 (de) *	1996-10-29	2002-03-15	Merck & Co Inc	Verfahren zur kristallisation von losartan
IT1295405B1 (it)	1997-09-30	1999-05-12	Merck Sharp & Dohme Italia S P	Uso di un antagonista recettoriale di angiotensina ii per la preparazione di farmaci per aumentare il tasso di sopravvivenza di
DE19916222A1 (de) *	1999-04-10	2000-10-19	Aventis Res & Tech Gmbh & Co	Verfahren zur Herstellung von Biarylen
JP4507294B2 (ja) *	1999-05-27	2010-07-21	チッソ株式会社	ビアリール誘導体の製造方法
JP2001226372A (ja)	1999-12-06	2001-08-21	Sumika Fine Chemicals Co Ltd	ロサルタンの結晶性または結晶化された酸付加塩およびロサルタンの精製方法
HU222773B1 (hu) *	2000-04-21	2003-10-28	Richter Gedeon Vegyészeti Gyár Rt.	Eljárás egy ismert tetrazolszármazék előállítására
JP2004520446A (ja) *	2001-05-18	2004-07-08	オーロビンドファーマリミテッド	ロサルタンカリウムの結晶化方法
DE602004029982D1 (de) *	2003-01-30	2010-12-23	Lek Pharmaceuticals	Herstellung eines neuen pharmazeutisch geeigneten losartan-salzes und von seinen formen mittels neuer reinigungs- und isolationsverfahren
US7345071B2 (en)	2003-05-07	2008-03-18	Ipca Laboratories Limited	Process for the synthesis of Losartan potassium
WO2005014560A1 (en) *	2003-08-08	2005-02-17	Dipharma S.P.A.	A process for the preparation of phenyltetrazole derivatives
ITMI20032069A1 (it) *	2003-10-23	2005-04-24	Dinamite Dipharma S P A In Forma A Bbreviata Diph	Procedimento per la preparazione di derivati benzilmidazolici.
DE102004060699A1 (de) *	2004-12-16	2006-06-22	Ratiopharm Gmbh	Verfahren zur Herstellung von Candesartan
FR2879601B1 (fr) *	2004-12-22	2007-01-19	Galderma Res & Dev	Nouveaux composes derives d'acide phenyl-boronique et leur procede de preparation
EP1833801B9 (de) *	2004-12-22	2009-02-25	Algry Quimica, S.L	Zwischenprodukte für die herstellung von antagonisten des angiotensin-ii-rezeptors
US20070117987A1 (en) *	2005-07-05	2007-05-24	Viviana Braude	Process for preparing valsartan
ES2300175B1 (es) *	2006-02-14	2009-06-08	Inke, S.A.	Procedimiento para la obtencion de intermedios utiles en la obtencion de un compuesto farmaceuticamente activo.
CN101812029B (zh) *	2010-04-29	2012-02-15	南通市华峰化工有限责任公司	5-卤代直链烷基四氮唑的生产方法
CN105906614A (zh) *	2016-05-12	2016-08-31	山东罗欣药业集团股份有限公司	一种奥美沙坦酯的制备方法
WO2018002673A1 (en)	2016-07-01	2018-01-04	N4 Pharma Uk Limited	Novel formulations of angiotensin ii receptor antagonists
CN114181048B (zh) *	2021-12-20	2024-06-21	宁夏清研高分子新材料有限公司	一种高产率的4-氟联苯酚的制备方法

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US4820843A (en) *	1987-05-22	1989-04-11	E. I. Du Pont De Nemours And Company	Tetrazole intermediates to antihypertensive compounds
CA1338238C (en) *	1988-01-07	1996-04-09	David John Carini	Angiotensin ii receptor blocking imidazoles and combinations thereof with diuretics and nsaids
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
IE914572A1 (en) *	1991-01-17	1992-07-29	Zeneca Ltd	Chemical process
US5164403A (en) *	1991-04-05	1992-11-17	G. D. Searle & Co.	N-arylheteroarylalkyl imidazol-2-one compounds for treatment of circulatory disorders
US5155117A (en) *	1991-04-12	1992-10-13	G. D. Searle & Co.	1-arylheteroarylalkyl substituted-1h-1,2,4-triazole compounds for treatment of circulatory disorders
US5149699A (en) *	1991-10-24	1992-09-22	American Home Products Corporation	Substituted pyridopyrimidines useful as antgiotensin II antagonists
TW226375B (de) *	1991-10-24	1994-07-11	American Home Prod
FR2688505B1 (fr) *	1992-03-16	1994-05-06	Synthelabo	Nouveau procede de preparation de 4-pyrimidinones.
FR2688507B1 (fr) *	1992-03-16	1994-05-06	Synthelabo	Derives de l'acide tetrazolylbenzeneboronique, leur preparation et leur utilisation comme intermediaires de synthese.
US5655009A (en) *	1992-03-19	1997-08-05	Fujitsu Limited	Modem unit

1992
- 1992-11-18 CA CA002123900A patent/CA2123900C/en not_active Expired - Lifetime
- 1992-11-18 DE DE69233208T patent/DE69233208T2/de not_active Expired - Lifetime
- 1992-11-18 KR KR1019940701677A patent/KR100212257B1/ko not_active IP Right Cessation
- 1992-11-18 CZ CZ941205A patent/CZ283954B6/cs not_active IP Right Cessation
- 1992-11-18 ES ES93900550T patent/ES2203614T3/es not_active Expired - Lifetime
- 1992-11-18 DE DE69233734T patent/DE69233734D1/de not_active Expired - Lifetime
- 1992-11-18 JP JP5509518A patent/JPH08500323A/ja not_active Expired - Lifetime
- 1992-11-18 AT AT03018662T patent/ATE395341T1/de active
- 1992-11-18 AU AU31792/93A patent/AU665388B2/en not_active Expired
- 1992-11-18 WO PCT/US1992/009979 patent/WO1993010106A1/en active IP Right Grant
- 1992-11-18 SK SK579-94A patent/SK280887B6/sk not_active IP Right Cessation
- 1992-11-18 DK DK93900550T patent/DK0643704T3/da active
- 1992-11-18 EP EP93900550A patent/EP0643704B1/de not_active Expired - Lifetime
- 1992-11-18 EP EP03018662A patent/EP1384717B1/de not_active Expired - Lifetime
- 1992-11-18 AT AT93900550T patent/ATE250043T1/de active
1994
- 1994-05-17 FI FI942282A patent/FI112945B/fi not_active IP Right Cessation
- 1994-05-18 NO NO941857A patent/NO307932B1/no not_active IP Right Cessation
1999
- 1999-01-25 KR KR1019997000625A patent/KR100212405B1/ko active

Also Published As

Publication number	Publication date
AU3179293A (en)	1993-06-15
NO307932B1 (no)	2000-06-19
DE69233734D1 (de)	2008-06-26
KR100212257B1 (ko)	1999-08-02
JPH08500323A (ja)	1996-01-16
EP1384717A3 (de)	2004-02-04
NO941857D0 (no)	1994-05-18
FI942282A0 (fi)	1994-05-17
ATE395341T1 (de)	2008-05-15
ES2203614T3 (es)	2004-04-16
CA2123900C (en)	1998-07-14
ATE250043T1 (de)	2003-10-15
SK280887B6 (sk)	2000-09-12
CA2123900A1 (en)	1993-05-27
DK0643704T3 (da)	2004-01-19
EP0643704A1 (de)	1995-03-22
NO941857L (no)	1994-07-18
SK57994A3 (en)	1995-02-08
CZ120594A3 (en)	1995-02-15
EP1384717B1 (de)	2008-05-14
KR100212405B1 (ko)	2000-03-15
FI942282A (fi)	1994-05-17
AU665388B2 (en)	1996-01-04
DE69233208D1 (de)	2003-10-23
EP0643704A4 (en)	1995-04-12
CZ283954B6 (cs)	1998-07-15
DE69233208T2 (de)	2004-07-08
WO1993010106A1 (en)	1993-05-27
EP1384717A2 (de)	2004-01-28
EP0643704B1 (de)	2003-09-17

Legal Events

Date	Code	Title	Description
2012-12-20	MA	Patent expired

Publication	Publication Date	Title
FI112945B (fi)	2004-02-13	Tetratsolyylifenyyliboorihappovälituotteita AII-reseptoriantagonistien synteesiä varten
US5130439A (en)	1992-07-14	Tetrazolylphenylboronic acid intermediates for the synthesis of AII receptor antagonists
US5310928A (en)	1994-05-10	Process for preparing biphenyltetrazole compounds
JP2008516005A (ja)	2008-05-15	レトロゾールの改良された調製方法
US5206374A (en)	1993-04-27	Process for preparing tetrazolylphenylboronic acid intermediates
JP2803905B2 (ja)	1998-09-24	Ａ▲ｉｉ▼受容体アンタゴニストの合成のための中間体化合物の製法
US4127587A (en)	1978-11-28	Triazolylbenzophenones
US5294617A (en)	1994-03-15	Angiotensin II receptor blocking 2,3,6 substituted quinazolinones
US3481920A (en)	1969-12-02	Azetidinones
JPH101467A (ja)	1998-01-06	ビフェニルアミジン誘導体
US4104278A (en)	1978-08-01	Process for the production of compounds with antiphlogistic activity
US5382672A (en)	1995-01-17	Preparation of derivatives of benzeneborinic acid
KR101113791B1 (ko)	2012-02-27	신규한 포타슘 아지도아릴트리플루오로보레이트 유도체 및 그 제조방법
EP0329691B1 (de)	1991-11-21	Cardiotonische imidazolylphenylpyrrol-2-one
EP1471058B1 (de)	2007-04-11	Verfahren zur herstellung einer 1,2,3-triazolverbindung
JPH0229672B2 (ja)	1990-07-02	11chikann55merukaputootetorazoorunoseizoho
Liu et al.	2022	SmI2-mediated intermolecular addition–elimination of piperidine and pyrrolidine N-α-radicals with arylacetylene sulfones
KR20100110438A (ko)	2010-10-13	올메살탄의 신규한 에스테르 화합물, 이의 중간체, 이의 제조방법 및 이를 포함하는 조성물
JPS5832866A (ja)	1983-02-25	光学活性２−オキソイミダゾリジン−４−カルボン酸誘導体の製法
JPS6044311B2 (ja)	1985-10-02	ウラシル誘導体の製法
JPH0456029B2 (de)	1992-09-07
JPH09509185A (ja)	1997-09-16	６−アリールオキシメチル−１−ヒドロキシ−４−メチル−２−ピリドンの製法
JPS60142983A (ja)	1985-07-29	複素環式化合物
EP0604259A1 (de)	1994-06-29	2-(Chinoline-6-yl-methyl)-4H-imidazol-4-one Derivate als Angiotensin II Antagoniste
JPH09323991A (ja)	1997-12-16	新規カルボキシメチリデンシクロヘプトイミダゾール誘導体及びその製造方法並びにこれを含有する薬剤