JP3001298B2 - ビフエニルカルボニトリルの製造方法 - Google Patents
ビフエニルカルボニトリルの製造方法Info
- Publication number
- JP3001298B2 JP3001298B2 JP3199442A JP19944291A JP3001298B2 JP 3001298 B2 JP3001298 B2 JP 3001298B2 JP 3199442 A JP3199442 A JP 3199442A JP 19944291 A JP19944291 A JP 19944291A JP 3001298 B2 JP3001298 B2 JP 3001298B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- alkyl
- group
- palladium
- 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 - Fee Related
Links
- 238000004519 manufacturing process Methods 0.000 title abstract description 8
- WLPATYNQCGVFFH-UHFFFAOYSA-N 2-phenylbenzonitrile Chemical compound N#CC1=CC=CC=C1C1=CC=CC=C1 WLPATYNQCGVFFH-UHFFFAOYSA-N 0.000 title description 4
- 238000000034 method Methods 0.000 claims abstract description 32
- 150000001639 boron compounds Chemical class 0.000 claims abstract 3
- -1 methoxy, ethoxy Chemical group 0.000 claims description 70
- 150000001875 compounds Chemical class 0.000 claims description 64
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 24
- 239000002904 solvent Substances 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 239000003054 catalyst Substances 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 239000002585 base Substances 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000001153 fluoro group Chemical group F* 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 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 12
- 125000001246 bromo group Chemical group Br* 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 10
- 229910052796 boron Inorganic materials 0.000 claims description 10
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 231100000252 nontoxic Toxicity 0.000 claims description 9
- 230000003000 nontoxic effect Effects 0.000 claims description 9
- 125000006239 protecting group Chemical group 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- 239000003999 initiator Substances 0.000 claims description 7
- 125000002346 iodo group Chemical group I* 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 claims description 6
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 239000007858 starting material Substances 0.000 claims description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 5
- VEQPNABPJHWNSG-UHFFFAOYSA-N Nickel(2+) Chemical compound [Ni+2] VEQPNABPJHWNSG-UHFFFAOYSA-N 0.000 claims description 5
- BRTALTYTFFNPAC-UHFFFAOYSA-N boroxin Chemical group B1OBOBO1 BRTALTYTFFNPAC-UHFFFAOYSA-N 0.000 claims description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 5
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 4
- HVLLSGMXQDNUAL-UHFFFAOYSA-N triphenyl phosphite Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 HVLLSGMXQDNUAL-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 3
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- BJUSKQNPSWYMEI-UHFFFAOYSA-N azido(triphenyl)stannane Chemical compound C=1C=CC=CC=1[Sn](C=1C=CC=CC=1)(N=[N+]=[N-])C1=CC=CC=C1 BJUSKQNPSWYMEI-UHFFFAOYSA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 2
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 claims description 2
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 claims description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 claims description 2
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 claims description 2
- ZBRJXVVKPBZPAN-UHFFFAOYSA-L nickel(2+);triphenylphosphane;dichloride Chemical compound [Cl-].[Cl-].[Ni+2].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 ZBRJXVVKPBZPAN-UHFFFAOYSA-L 0.000 claims description 2
- KFBKRCXOTTUAFS-UHFFFAOYSA-N nickel;triphenylphosphane Chemical group [Ni].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 KFBKRCXOTTUAFS-UHFFFAOYSA-N 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 7
- 150000002500 ions Chemical class 0.000 claims 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims 1
- 150000001540 azides Chemical class 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 150000002815 nickel Chemical group 0.000 claims 1
- 229910052759 nickel Inorganic materials 0.000 claims 1
- 102000005862 Angiotensin II Human genes 0.000 abstract description 19
- 101800000733 Angiotensin-2 Proteins 0.000 abstract description 19
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound 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 abstract description 19
- 229950006323 angiotensin ii Drugs 0.000 abstract description 19
- 230000008569 process Effects 0.000 abstract description 10
- 150000002460 imidazoles Chemical class 0.000 abstract description 3
- 230000002401 inhibitory effect Effects 0.000 abstract description 3
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 abstract description 3
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 abstract description 3
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 abstract description 2
- 150000002825 nitriles Chemical class 0.000 abstract description 2
- 239000002333 angiotensin II receptor antagonist Substances 0.000 abstract 1
- 238000006555 catalytic reaction Methods 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 13
- 239000007787 solid Substances 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
- 238000010992 reflux Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- ZGQVZLSNEBEHFN-UHFFFAOYSA-N 2-(4-methylphenyl)benzonitrile Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1C#N ZGQVZLSNEBEHFN-UHFFFAOYSA-N 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 150000003248 quinolines Chemical class 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 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 description 4
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 3
- AFMPMSCZPVNPEM-UHFFFAOYSA-N 2-bromobenzonitrile Chemical compound BrC1=CC=CC=C1C#N AFMPMSCZPVNPEM-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000005530 alkylenedioxy group Chemical group 0.000 description 3
- 230000008485 antagonism Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 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 3
- BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 description 2
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 2
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 2
- RSAZIKNNSSKYHN-UHFFFAOYSA-N 2-(4-methylphenyl)benzene-1,3-dicarbonitrile Chemical compound C1=CC(C)=CC=C1C1=C(C#N)C=CC=C1C#N RSAZIKNNSSKYHN-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 2
- BLENHSITVMPXJB-UHFFFAOYSA-N 2-methyl-3h-quinolin-4-one Chemical compound C1=CC=C2C(=O)CC(C)=NC2=C1 BLENHSITVMPXJB-UHFFFAOYSA-N 0.000 description 2
- ZDCOSHSTGKGXBA-UHFFFAOYSA-N 2-methyl-4-[[4-[2-(2-trityltetrazol-5-yl)phenyl]phenyl]methoxy]quinoline Chemical compound C=12C=CC=CC2=NC(C)=CC=1OCC(C=C1)=CC=C1C1=CC=CC=C1C(=N1)N=NN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 ZDCOSHSTGKGXBA-UHFFFAOYSA-N 0.000 description 2
- GDPFHLZDDWJSSV-UHFFFAOYSA-N 2-methyl-4-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methoxy]quinoline;hydrochloride Chemical compound Cl.C=12C=CC=CC2=NC(C)=CC=1OCC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 GDPFHLZDDWJSSV-UHFFFAOYSA-N 0.000 description 2
- CTTUUXGJIWMJHV-UHFFFAOYSA-N 2-methyl-6-phenylbenzonitrile Chemical compound CC1=CC=CC(C=2C=CC=CC=2)=C1C#N CTTUUXGJIWMJHV-UHFFFAOYSA-N 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 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 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
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- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 150000003109 potassium Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000011165 process development Methods 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003536 tetrazoles Chemical group 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/50—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
-
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Turning (AREA)
- Glass Compositions (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Magnetic Resonance Imaging Apparatus (AREA)
- Air Bags (AREA)
- Electrotherapy Devices (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB909017482A GB9017482D0 (en) | 1990-08-09 | 1990-08-09 | Manufacturing process |
| GB9017482:2 | 1990-08-09 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH04253949A JPH04253949A (ja) | 1992-09-09 |
| JP3001298B2 true JP3001298B2 (ja) | 2000-01-24 |
Family
ID=10680408
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3199442A Expired - Fee Related JP3001298B2 (ja) | 1990-08-09 | 1991-08-08 | ビフエニルカルボニトリルの製造方法 |
Country Status (23)
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE117294T1 (de) * | 1989-08-11 | 1995-02-15 | Ici Plc | Chinolin-derivate, verfahren zu ihrer herstellung und ihre anwendung als arzneimittel. |
| DE4132632A1 (de) * | 1991-10-01 | 1993-04-08 | Bayer Ag | Substituierte imidazolyl-propensaeurederivate |
| DE4132633A1 (de) * | 1991-10-01 | 1993-04-08 | Bayer Ag | Cyclisch substituierte imidazolyl-propensaeurederivate |
| DE4132631A1 (de) * | 1991-10-01 | 1993-04-08 | Bayer Ag | Imidazolyl-propensaeurederivate |
| US5310928A (en) * | 1991-11-18 | 1994-05-10 | E. I. Du Pont De Nemours And Company | Process for preparing biphenyltetrazole compounds |
| US5206374A (en) * | 1991-11-18 | 1993-04-27 | E. I. Du Pont De Nemours And Company | Process for preparing tetrazolylphenylboronic acid intermediates |
| FR2688507B1 (fr) * | 1992-03-16 | 1994-05-06 | Synthelabo | Derives de l'acide tetrazolylbenzeneboronique, leur preparation et leur utilisation comme intermediaires de synthese. |
| FR2689887B1 (fr) * | 1992-04-13 | 1995-06-23 | Sanofi Elf | Procede de preparation d'un derive de biphenyle. |
| FR2696746B1 (fr) * | 1992-10-12 | 1994-11-18 | Synthelabo | Dérivés de l'acide benzèneborinique, leur préparation et leur utilisation comme intermédiaires de synthèse. |
| DE4423061C1 (de) | 1994-07-01 | 1996-01-18 | Hoechst Ag | Verfahren zur Herstellung von Biphenylen mit Palladacyclen als Katalysatoren |
| DE4426671A1 (de) * | 1994-07-28 | 1996-02-01 | Hoechst Ag | Verfahren zur Kreuzkupplung von aromatischen Borverbindungen mit aromatischen Halogenverbindungen oder Perfluoralkylsulfonaten |
| KR100354802B1 (ko) * | 1994-10-20 | 2002-12-26 | 한국화학연구원 | 테트라졸유도체의제조방법 |
| JP2928982B2 (ja) | 1994-10-27 | 1999-08-03 | 住化ファインケム株式会社 | ４’−ブロモメチル−２−シアノビフェニルの製造法 |
| DE19620023C2 (de) * | 1996-05-17 | 2001-03-08 | Celanese Chem Europe Gmbh | Verfahren zur Herstellung von Phosphinat- oder Phosphonatgruppen enthaltenden tertiären Phosphanen und neue Phosphinatgruppen enthaltende tertiäre Phosphane |
| US5922898A (en) * | 1997-04-08 | 1999-07-13 | Catalytica Pharmaceuticals, Inc. | Process for preparing biaryl compounds |
| US6194599B1 (en) | 1997-04-08 | 2001-02-27 | Catalytica, Inc. | Process for preparing biaryl compounds |
| JP2002506836A (ja) | 1998-03-18 | 2002-03-05 | チバ スペシャルティ ケミカルズ ホールディング インコーポレーテッド | パラジウム触媒によるカップリング反応 |
| US6962999B2 (en) | 2001-07-25 | 2005-11-08 | Pharmacore, Inc. | Process for preparing unsymmetrical biaryls and alkylated aromatic compounds from arylnitriles |
| DE10211597A1 (de) | 2002-03-15 | 2003-10-02 | Merck Patent Gmbh | Verfahren zur Herstellung von Ringverbindungen |
| ATE321039T1 (de) | 2002-04-29 | 2006-04-15 | Teva Pharma | Verfahren zur herstellung von losartan und losartan-kaliumsalz |
| PT1535901E (pt) | 2002-06-12 | 2008-04-10 | Sumitomo Chemical Co | Processo para a produção de 4'-bromometil-2-cianobifenilo |
| US7105467B2 (en) | 2003-07-08 | 2006-09-12 | Pharmacore, Inc. | Nickel catalyzed cross-coupling reactions between organomagnesium compounds and anisole derivatives |
| US7105707B2 (en) | 2003-12-17 | 2006-09-12 | Pharmacore, Inc. | Process for preparing alkynyl-substituted aromatic and heterocyclic compounds |
| JP2006151946A (ja) * | 2004-04-30 | 2006-06-15 | Konishi Kagaku Ind Co Ltd | ジアリール誘導体の製造方法 |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| ES2393885T7 (es) | 2007-06-04 | 2014-01-30 | Synergy Pharmaceuticals Inc. | Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos |
| CA2726917C (en) | 2008-06-04 | 2018-06-26 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| AU2009270833B2 (en) | 2008-07-16 | 2015-02-19 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| MX2012002301A (es) * | 2009-08-31 | 2012-03-29 | Bayer Cropscience Ag | Procedimiento de tetraarilborato para la preparacion de bifenilos sustituidos. |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| US9708367B2 (en) | 2013-03-15 | 2017-07-18 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase and their uses |
| JP2016514670A (ja) | 2013-03-15 | 2016-05-23 | シナジー ファーマシューティカルズ インコーポレイテッド | 他の薬物と組み合わせたグアニル酸シクラーゼ受容体アゴニスト |
| EA201592263A1 (ru) | 2013-06-05 | 2016-05-31 | Синерджи Фармасьютикалз, Инк. | Ультрачистые агонисты гуанилатциклазы c, способ их получения и использования |
| JP5975081B2 (ja) * | 2013-09-30 | 2016-08-23 | ダイキン工業株式会社 | 含フッ素ビアリール化合物の製造方法 |
| CN119677720A (zh) | 2021-11-02 | 2025-03-21 | 弗拉雷治疗公司 | Pparg反向激动剂及其用途 |
| CN117623932A (zh) * | 2023-11-30 | 2024-03-01 | 江苏康恒化工有限公司 | 中间体2，2’-二硝基联苯的合成方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1334092C (en) * | 1986-07-11 | 1995-01-24 | David John Carini | Angiotensin ii receptor blocking imidazoles |
| EP0395666B1 (en) * | 1987-10-19 | 1994-05-04 | The Secretary of State for Defence in Her Britannic Majesty's Government of the United Kingdom of Great Britain and | Laterally cyano- and fluoro-substituted terphenyls |
| CA1338238C (en) * | 1988-01-07 | 1996-04-09 | David John Carini | Angiotensin ii receptor blocking imidazoles and combinations thereof with diuretics and nsaids |
| ATE117294T1 (de) * | 1989-08-11 | 1995-02-15 | Ici Plc | Chinolin-derivate, verfahren zu ihrer herstellung und ihre anwendung als arzneimittel. |
-
1990
- 1990-08-09 GB GB909017482A patent/GB9017482D0/en active Pending
-
1991
- 1991-07-15 ZW ZW95/91A patent/ZW9591A1/xx unknown
- 1991-07-16 IL IL98862A patent/IL98862A0/xx unknown
- 1991-07-16 AU AU80436/91A patent/AU646473B2/en not_active Ceased
- 1991-07-16 ZA ZA915566A patent/ZA915566B/xx unknown
- 1991-07-16 GB GB919115244A patent/GB9115244D0/en active Pending
- 1991-07-18 CA CA002047369A patent/CA2047369A1/en not_active Abandoned
- 1991-07-18 NZ NZ239026A patent/NZ239026A/en unknown
- 1991-07-24 HU HU912481A patent/HU207841B/hu not_active IP Right Cessation
- 1991-07-29 CN CN91105206A patent/CN1059516A/zh active Pending
- 1991-07-30 FI FI913640A patent/FI913640A7/fi unknown
- 1991-08-02 CS CS912413A patent/CS241391A3/cs unknown
- 1991-08-05 EP EP91307184A patent/EP0470795B2/en not_active Expired - Lifetime
- 1991-08-05 AT AT91307184T patent/ATE117672T1/de active
- 1991-08-05 ES ES91307184T patent/ES2067159T3/es not_active Expired - Lifetime
- 1991-08-05 DE DE69106977T patent/DE69106977T3/de not_active Expired - Fee Related
- 1991-08-08 RU SU915001352A patent/RU2026285C1/ru active
- 1991-08-08 KR KR1019910013873A patent/KR920004337A/ko not_active Withdrawn
- 1991-08-08 PL PL29137091A patent/PL291370A1/xx unknown
- 1991-08-08 PT PT98608A patent/PT98608A/pt not_active Application Discontinuation
- 1991-08-08 JP JP3199442A patent/JP3001298B2/ja not_active Expired - Fee Related
- 1991-08-08 NO NO913086A patent/NO174502B/no unknown
- 1991-08-09 YU YU137891A patent/YU137891A/sh unknown
- 1991-08-12 TW TW080106352A patent/TW198710B/zh active
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