BRPI0710473A2 - ácidos 4-fenil-tiazol-5-carboxìlicos e amidas de ácido 4-fenil-tiazol-5-carboxìlico como inibidores de plk1 - Google Patents

Info

Publication number

BRPI0710473A2

BRPI0710473A2 BRPI0710473-1A BRPI0710473A BRPI0710473A2 BR PI0710473 A2 BRPI0710473 A2 BR PI0710473A2 BR PI0710473 A BRPI0710473 A BR PI0710473A BR PI0710473 A2 BRPI0710473 A2 BR PI0710473A2

Authority

BR

Brazil

Prior art keywords

carboxylic acid

benzoimidazol

phenyl

formula

dimethoxy

Prior art date

2006-02-27

Links

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• 239000003112 inhibitor Substances 0.000 title abstract description 19
• NGTZFWMOTDGMKO-UHFFFAOYSA-N 4-phenyl-1,3-thiazole-5-carboxylic acid Chemical class S1C=NC(C=2C=CC=CC=2)=C1C(=O)O NGTZFWMOTDGMKO-UHFFFAOYSA-N 0.000 title abstract description 3
• ZLKBOBCOZBUZSF-UHFFFAOYSA-N 4-phenyl-1,3-thiazole-5-carboxamide Chemical class S1C=NC(C=2C=CC=CC=2)=C1C(=O)N ZLKBOBCOZBUZSF-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 189
• 238000000034 method Methods 0.000 claims abstract description 81
• 102100031463 Serine/threonine-protein kinase PLK1 Human genes 0.000 claims abstract description 31
• 108010056274 polo-like kinase 1 Proteins 0.000 claims abstract description 31
• 150000003839 salts Chemical class 0.000 claims abstract description 23
• -1 2- (8H-5,7-dioxa-1,3-diaza-cyclopenta [b] naphthalen-3-yl) -4-phenyl 2- (5-chloro-benzoimidazol-1-yl) -4-phenyl-thiazol-5-carboxylic acid Chemical compound 0.000 claims description 118
• 239000002253 acid Substances 0.000 claims description 50
• 125000000217 alkyl group Chemical group 0.000 claims description 45
• 239000000203 mixture Substances 0.000 claims description 43
• 125000000623 heterocyclic group Chemical group 0.000 claims description 26
• 229910052736 halogen Inorganic materials 0.000 claims description 22
• 239000001257 hydrogen Substances 0.000 claims description 21
• 229910052739 hydrogen Inorganic materials 0.000 claims description 21
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
• 125000003545 alkoxy group Chemical group 0.000 claims description 19
• 150000002367 halogens Chemical class 0.000 claims description 18
• 125000004432 carbon atom Chemical group C* 0.000 claims description 17
• 239000000543 intermediate Substances 0.000 claims description 17
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
• 230000000694 effects Effects 0.000 claims description 15
• 206010028980 Neoplasm Diseases 0.000 claims description 14
• 125000003118 aryl group Chemical group 0.000 claims description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
• 229910052757 nitrogen Inorganic materials 0.000 claims description 11
• ASNYTHITDPHAHV-UHFFFAOYSA-N 4-(3-chlorophenyl)-2-(5,6-dimethoxybenzimidazol-1-yl)-1,3-thiazole-5-carboxylic acid Chemical compound C1=2C=C(OC)C(OC)=CC=2N=CN1C(SC=1C(O)=O)=NC=1C1=CC=CC(Cl)=C1 ASNYTHITDPHAHV-UHFFFAOYSA-N 0.000 claims description 10
• 125000004429 atom Chemical group 0.000 claims description 10
• 125000003107 substituted aryl group Chemical group 0.000 claims description 10
• 230000008569 process Effects 0.000 claims description 9
• 201000010099 disease Diseases 0.000 claims description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
• 239000003814 drug Substances 0.000 claims description 8
• 229910052760 oxygen Inorganic materials 0.000 claims description 8
• 125000001424 substituent group Chemical group 0.000 claims description 8
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
• 239000001301 oxygen Substances 0.000 claims description 7
• 229910052717 sulfur Inorganic materials 0.000 claims description 7
• 239000011593 sulfur Substances 0.000 claims description 7
• 201000011510 cancer Diseases 0.000 claims description 6
• UKLMWNNCZHYWNQ-UHFFFAOYSA-N 2-(5-methylbenzimidazol-1-yl)-4-phenyl-1,3-thiazole-5-carboxylic acid Chemical compound C1=NC2=CC(C)=CC=C2N1C(SC=1C(O)=O)=NC=1C1=CC=CC=C1 UKLMWNNCZHYWNQ-UHFFFAOYSA-N 0.000 claims description 5
• 150000002431 hydrogen Chemical class 0.000 claims description 5
• GPSDUZXPYCFOSQ-UHFFFAOYSA-N m-toluic acid Chemical compound CC1=CC=CC(C(O)=O)=C1 GPSDUZXPYCFOSQ-UHFFFAOYSA-N 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• CMRKDXGOFRFBFT-UHFFFAOYSA-N 5-chloro-6-methyl-1h-benzimidazole Chemical compound C1=C(Cl)C(C)=CC2=C1N=CN2 CMRKDXGOFRFBFT-UHFFFAOYSA-N 0.000 claims description 4
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 125000005529 alkyleneoxy group Chemical group 0.000 claims description 4
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
• OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 4
• GESAUXAKNJZEKH-UHFFFAOYSA-N 2-(5,6-dimethoxybenzimidazol-1-yl)-4-(3-fluorophenyl)-1,3-thiazole-5-carboxylic acid Chemical compound C1=2C=C(OC)C(OC)=CC=2N=CN1C(SC=1C(O)=O)=NC=1C1=CC=CC(F)=C1 GESAUXAKNJZEKH-UHFFFAOYSA-N 0.000 claims description 3
• AYJRBUKJAAYPMJ-UHFFFAOYSA-N 2-(5,6-dimethoxybenzimidazol-1-yl)-4-phenyl-1,3-thiazole-5-carboxylic acid Chemical compound C1=2C=C(OC)C(OC)=CC=2N=CN1C(SC=1C(O)=O)=NC=1C1=CC=CC=C1 AYJRBUKJAAYPMJ-UHFFFAOYSA-N 0.000 claims description 3
• RMLVXIDTNWGOGL-UHFFFAOYSA-N 2-(5-chloro-6-methylbenzimidazol-1-yl)-4-phenyl-1,3-thiazole-5-carboxylic acid Chemical compound C1=NC=2C=C(Cl)C(C)=CC=2N1C(SC=1C(O)=O)=NC=1C1=CC=CC=C1 RMLVXIDTNWGOGL-UHFFFAOYSA-N 0.000 claims description 3
• UEGUPKZLQHKAKO-UHFFFAOYSA-N 2-(5-methoxy-6-methylbenzimidazol-1-yl)-4-phenyl-1,3-thiazole-5-carboxylic acid Chemical compound C1=2C=C(C)C(OC)=CC=2N=CN1C(SC=1C(O)=O)=NC=1C1=CC=CC=C1 UEGUPKZLQHKAKO-UHFFFAOYSA-N 0.000 claims description 3
• ZMGWBKZUFTUTEA-UHFFFAOYSA-N 2-(6-chloro-5-fluorobenzimidazol-1-yl)-4-phenyl-1,3-thiazole-5-carboxylic acid Chemical compound OC(=O)C=1SC(N2C3=CC(Cl)=C(F)C=C3N=C2)=NC=1C1=CC=CC=C1 ZMGWBKZUFTUTEA-UHFFFAOYSA-N 0.000 claims description 3
• RWWYSPVYHFYQEI-UHFFFAOYSA-N 2-(benzimidazol-1-yl)-4-phenyl-1,3-thiazole-5-carboxamide Chemical compound NC(=O)C=1SC(N2C3=CC=CC=C3N=C2)=NC=1C1=CC=CC=C1 RWWYSPVYHFYQEI-UHFFFAOYSA-N 0.000 claims description 3
• DYUPBENDIHQGHP-UHFFFAOYSA-N 4-(2-chlorophenyl)-2-(5,6-dimethoxybenzimidazol-1-yl)-1,3-thiazole-5-carboxylic acid Chemical compound C1=2C=C(OC)C(OC)=CC=2N=CN1C(SC=1C(O)=O)=NC=1C1=CC=CC=C1Cl DYUPBENDIHQGHP-UHFFFAOYSA-N 0.000 claims description 3
• 239000002671 adjuvant Substances 0.000 claims description 3
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 125000001188 haloalkyl group Chemical group 0.000 claims description 3
• QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 claims description 3
• PNKPQBBBXKMHCY-UHFFFAOYSA-N 2-(4-hydroxybenzimidazol-1-yl)-4-phenyl-1,3-thiazole-5-carboxylic acid Chemical compound OC(=O)C=1SC(N2C3=CC=CC(O)=C3N=C2)=NC=1C1=CC=CC=C1 PNKPQBBBXKMHCY-UHFFFAOYSA-N 0.000 claims description 2
• RYVMXWTXDWJVDB-UHFFFAOYSA-N 2-(5,6-dimethoxybenzimidazol-1-yl)-4-(3,4-dimethoxyphenyl)-1,3-thiazole-5-carboxylic acid Chemical compound C1=C(OC)C(OC)=CC=C1C1=C(C(O)=O)SC(N2C3=CC(OC)=C(OC)C=C3N=C2)=N1 RYVMXWTXDWJVDB-UHFFFAOYSA-N 0.000 claims description 2
• YPENMNILWSQOND-UHFFFAOYSA-N 2-(5,6-dimethoxybenzimidazol-1-yl)-4-(4-methylphenyl)-1,3-thiazole-5-carboxylic acid Chemical compound C1=2C=C(OC)C(OC)=CC=2N=CN1C(SC=1C(O)=O)=NC=1C1=CC=C(C)C=C1 YPENMNILWSQOND-UHFFFAOYSA-N 0.000 claims description 2
• JGFXBKCPGKLGOC-UHFFFAOYSA-N 2-(5,6-dimethoxybenzimidazol-1-yl)-n,n-dimethyl-4-phenyl-1,3-thiazole-5-carboxamide Chemical compound C1=2C=C(OC)C(OC)=CC=2N=CN1C(SC=1C(=O)N(C)C)=NC=1C1=CC=CC=C1 JGFXBKCPGKLGOC-UHFFFAOYSA-N 0.000 claims description 2
• PQSSBTQHZHXLJL-UHFFFAOYSA-N 4-(1,3-benzodioxol-5-yl)-2-(5,6-dimethoxybenzimidazol-1-yl)-1,3-thiazole-5-carboxylic acid Chemical compound C1=C2OCOC2=CC(C=2N=C(SC=2C(O)=O)N2C=NC=3C=C(C(=CC=32)OC)OC)=C1 PQSSBTQHZHXLJL-UHFFFAOYSA-N 0.000 claims description 2
• GXSMRZKLEMBKNV-UHFFFAOYSA-N 4-(3-chlorophenyl)-2-(5,6-dimethoxybenzimidazol-1-yl)-1,3-thiazole-5-carboxamide Chemical compound C1=2C=C(OC)C(OC)=CC=2N=CN1C(SC=1C(N)=O)=NC=1C1=CC=CC(Cl)=C1 GXSMRZKLEMBKNV-UHFFFAOYSA-N 0.000 claims description 2
• NSPIHQBVBFUKPO-UHFFFAOYSA-N 4-(3-chlorophenyl)-2-(5,6-dimethoxybenzimidazol-1-yl)-n-(1,3-thiazol-2-yl)-1,3-thiazole-5-carboxamide Chemical compound C1=2C=C(OC)C(OC)=CC=2N=CN1C(S1)=NC(C=2C=C(Cl)C=CC=2)=C1C(=O)NC1=NC=CS1 NSPIHQBVBFUKPO-UHFFFAOYSA-N 0.000 claims description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
• YQLVQWSSUDEOAJ-UHFFFAOYSA-N 2-(5-methoxybenzimidazol-1-yl)-4-phenyl-1,3-thiazole-5-carboxylic acid Chemical compound C1=NC2=CC(OC)=CC=C2N1C(SC=1C(O)=O)=NC=1C1=CC=CC=C1 YQLVQWSSUDEOAJ-UHFFFAOYSA-N 0.000 claims 2
• 125000005843 halogen group Chemical group 0.000 claims 2
• KKSARMOSVBRKOK-UHFFFAOYSA-N 2-(5,6-dimethoxybenzimidazol-1-yl)-4-phenyl-5-(2h-tetrazol-5-yl)-1,3-thiazole Chemical compound C1=2C=C(OC)C(OC)=CC=2N=CN1C(S1)=NC(C=2C=CC=CC=2)=C1C1=NN=NN1 KKSARMOSVBRKOK-UHFFFAOYSA-N 0.000 claims 1
• BLJVEZPCIIAHTC-UHFFFAOYSA-N 2-[6-(2-methoxyethoxy)benzimidazol-1-yl]-4-phenyl-1,3-thiazole-5-carboxylic acid Chemical compound C12=CC(OCCOC)=CC=C2N=CN1C(SC=1C(O)=O)=NC=1C1=CC=CC=C1 BLJVEZPCIIAHTC-UHFFFAOYSA-N 0.000 claims 1
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims 1
• ALPVNDFXSUBVFX-UHFFFAOYSA-N 4-(3-chlorophenyl)-2-(5,6-dimethoxybenzimidazol-1-yl)-1,3-thiazole Chemical compound ClC=1C=C(C=CC=1)C=1N=C(SC=1)N1C=NC2=C1C=C(C(=C2)OC)OC ALPVNDFXSUBVFX-UHFFFAOYSA-N 0.000 claims 1
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
• 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims 1
• 238000006243 chemical reaction Methods 0.000 description 143
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
• 239000007787 solid Substances 0.000 description 56
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 50
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
• 238000005160 1H NMR spectroscopy Methods 0.000 description 44
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 44
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
• 239000002904 solvent Substances 0.000 description 34
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 32
• MNUFHYBLHGNPSN-UHFFFAOYSA-N methyl 4-bromo-2-(5,6-dimethoxybenzimidazol-1-yl)-1,3-thiazole-5-carboxylate Chemical compound BrC1=C(C(=O)OC)SC(N2C3=CC(OC)=C(OC)C=C3N=C2)=N1 MNUFHYBLHGNPSN-UHFFFAOYSA-N 0.000 description 31
• 239000000243 solution Substances 0.000 description 30
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 28
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 27
• 239000000047 product Substances 0.000 description 26
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• 239000003153 chemical reaction reagent Substances 0.000 description 24
• 239000012442 inert solvent Substances 0.000 description 24
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
• 229910052763 palladium Inorganic materials 0.000 description 21
• 238000002360 preparation method Methods 0.000 description 21
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 20
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
• 238000010992 reflux Methods 0.000 description 20
• 235000019439 ethyl acetate Nutrition 0.000 description 19
• 239000002585 base Substances 0.000 description 18
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
• 230000015572 biosynthetic process Effects 0.000 description 16
• 150000002148 esters Chemical class 0.000 description 16
• 238000003786 synthesis reaction Methods 0.000 description 16
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 14
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 14
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
• 150000001556 benzimidazoles Chemical class 0.000 description 14
• 239000003054 catalyst Substances 0.000 description 14
• 235000019253 formic acid Nutrition 0.000 description 14
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
• 150000001408 amides Chemical class 0.000 description 13
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
• 230000003197 catalytic effect Effects 0.000 description 12
• GCYRUFVHYNWOFH-UHFFFAOYSA-N ethyl 2-chloro-4-phenyl-1,3-thiazole-5-carboxylate Chemical compound S1C(Cl)=NC(C=2C=CC=CC=2)=C1C(=O)OCC GCYRUFVHYNWOFH-UHFFFAOYSA-N 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• 239000000126 substance Substances 0.000 description 12
• 210000004027 cell Anatomy 0.000 description 11
• 238000002953 preparative HPLC Methods 0.000 description 11
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 10
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 10
• 239000003795 chemical substances by application Substances 0.000 description 10
• RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 9
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• 239000012876 carrier material Substances 0.000 description 9
• 238000005859 coupling reaction Methods 0.000 description 9
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 8
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
• 125000002947 alkylene group Chemical group 0.000 description 8
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
• 239000012043 crude product Substances 0.000 description 8
• 150000002576 ketones Chemical class 0.000 description 8
• 239000007788 liquid Substances 0.000 description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
• 150000002825 nitriles Chemical class 0.000 description 8
• 229910000104 sodium hydride Inorganic materials 0.000 description 8
• 239000012453 solvate Substances 0.000 description 8
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
• 230000009466 transformation Effects 0.000 description 8
• 229940086542 triethylamine Drugs 0.000 description 8
• 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
• BTWUUHKQHOSMIN-UHFFFAOYSA-N 5,6-dimethoxy-1h-benzimidazole Chemical compound C1=C(OC)C(OC)=CC2=C1NC=N2 BTWUUHKQHOSMIN-UHFFFAOYSA-N 0.000 description 7
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
• 150000001412 amines Chemical class 0.000 description 7
• 229910052794 bromium Inorganic materials 0.000 description 7
• 239000000460 chlorine Substances 0.000 description 7
• 239000007822 coupling agent Substances 0.000 description 7
• 238000004128 high performance liquid chromatography Methods 0.000 description 7
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
• 235000019341 magnesium sulphate Nutrition 0.000 description 7
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 238000006722 reduction reaction Methods 0.000 description 7
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
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