RU2459821C2 - Модуляторы киназы, ассоциированной с рецептором интерлейкина-1 - Google Patents

Info

Publication number

RU2459821C2

RU2459821C2 RU2009112598/04A RU2009112598A RU2459821C2 RU 2459821 C2 RU2459821 C2 RU 2459821C2 RU 2009112598/04 A RU2009112598/04 A RU 2009112598/04A RU 2009112598 A RU2009112598 A RU 2009112598A RU 2459821 C2 RU2459821 C2 RU 2459821C2

Authority

RU

Russia

Prior art keywords

benzo

alkyl

indazol

radical

ylamino

Prior art date

2006-09-07

Links

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• 102000006940 Interleukin-1 Receptor-Associated Kinases Human genes 0.000 title 1
• 108010072621 Interleukin-1 Receptor-Associated Kinases Proteins 0.000 title 1
• -1 amino, methoxy Chemical group 0.000 claims abstract description 197
• 150000001875 compounds Chemical class 0.000 claims abstract description 153
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 83
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 78
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 48
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 29
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 25
• 150000002367 halogens Chemical class 0.000 claims abstract description 25
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 16
• 125000002950 monocyclic group Chemical group 0.000 claims abstract description 14
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims abstract description 10
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims abstract description 9
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 9
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 7
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 7
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims abstract 5
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract 5
• 125000001424 substituent group Chemical group 0.000 claims description 36
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
• 229910052739 hydrogen Inorganic materials 0.000 claims description 14
• 206010028980 Neoplasm Diseases 0.000 claims description 9
• 201000011510 cancer Diseases 0.000 claims description 9
• 125000004076 pyridyl group Chemical group 0.000 claims description 9
• 206010040047 Sepsis Diseases 0.000 claims description 7
• 201000006417 multiple sclerosis Diseases 0.000 claims description 7
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
• 206010052779 Transplant rejections Diseases 0.000 claims description 6
• 208000026935 allergic disease Diseases 0.000 claims description 6
• 208000006673 asthma Diseases 0.000 claims description 6
• 201000004681 Psoriasis Diseases 0.000 claims description 5
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
• RSFJUAJAYHSBHD-UHFFFAOYSA-N 1-cyclohexyl-n-[5-(4-methoxypyridin-3-yl)-1h-indazol-3-yl]-5-(morpholin-4-ylmethyl)benzimidazol-2-amine Chemical compound COC1=CC=NC=C1C1=CC=C(NN=C2NC=3N(C4=CC=C(CN5CCOCC5)C=C4N=3)C3CCCCC3)C2=C1 RSFJUAJAYHSBHD-UHFFFAOYSA-N 0.000 claims description 4
• FETDUDQELDASEU-UHFFFAOYSA-N 3-[2-[[5-(4-methoxypyridin-3-yl)-1h-indazol-3-yl]amino]benzimidazol-1-yl]propan-1-ol Chemical compound COC1=CC=NC=C1C1=CC=C(NN=C2NC=3N(C4=CC=CC=C4N=3)CCCO)C2=C1 FETDUDQELDASEU-UHFFFAOYSA-N 0.000 claims description 4
• XNNSMLBQCJOFTI-UHFFFAOYSA-N 4-[5-(hydroxymethyl)-2-[[5-(4-methoxypyridin-3-yl)-1h-indazol-3-yl]amino]benzimidazol-1-yl]cyclohexan-1-ol Chemical compound COC1=CC=NC=C1C1=CC=C(NN=C2NC=3N(C4=CC=C(CO)C=C4N=3)C3CCC(O)CC3)C2=C1 XNNSMLBQCJOFTI-UHFFFAOYSA-N 0.000 claims description 4
• RCDOOVVHRGUAKF-UHFFFAOYSA-N [1-cyclohexyl-2-[[5-(4-methoxypyridin-3-yl)-1h-indazol-3-yl]amino]benzimidazol-5-yl]methanol Chemical compound COC1=CC=NC=C1C1=CC=C(NN=C2NC=3N(C4=CC=C(CO)C=C4N=3)C3CCCCC3)C2=C1 RCDOOVVHRGUAKF-UHFFFAOYSA-N 0.000 claims description 4
• PGSYKHBFXWTSGP-UHFFFAOYSA-N [2-[[5-(4-methoxypyridin-3-yl)-1h-indazol-3-yl]amino]-1-phenylbenzimidazol-5-yl]methanol Chemical compound COC1=CC=NC=C1C1=CC=C(NN=C2NC=3N(C4=CC=C(CO)C=C4N=3)C=3C=CC=CC=3)C2=C1 PGSYKHBFXWTSGP-UHFFFAOYSA-N 0.000 claims description 4
• MYSIISRDNSWBDA-UHFFFAOYSA-N ethyl 1-(4-hydroxycyclohexyl)-2-[[5-(4-methoxypyridin-3-yl)-1h-indazol-3-yl]amino]benzimidazole-5-carboxylate Chemical compound N=1NC2=CC=C(C=3C(=CC=NC=3)OC)C=C2C=1NC1=NC2=CC(C(=O)OCC)=CC=C2N1C1CCC(O)CC1 MYSIISRDNSWBDA-UHFFFAOYSA-N 0.000 claims description 4
• CFSUYKKSSWNBCA-UHFFFAOYSA-N n-cyclopentyl-1-(4-hydroxycyclohexyl)-2-[[5-(2-methoxyphenyl)-1h-indazol-3-yl]amino]benzimidazole-5-carboxamide Chemical compound COC1=CC=CC=C1C1=CC=C(NN=C2NC=3N(C4=CC=C(C=C4N=3)C(=O)NC3CCCC3)C3CCC(O)CC3)C2=C1 CFSUYKKSSWNBCA-UHFFFAOYSA-N 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• VTJFVOQGGHESGO-UHFFFAOYSA-N 1-cyclohexyl-n-[5-(4-methoxypyridin-3-yl)-1h-indazol-3-yl]-5-(piperidin-1-ylmethyl)benzimidazol-2-amine Chemical compound COC1=CC=NC=C1C1=CC=C(NN=C2NC=3N(C4=CC=C(CN5CCCCC5)C=C4N=3)C3CCCCC3)C2=C1 VTJFVOQGGHESGO-UHFFFAOYSA-N 0.000 claims description 3
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
• 208000024827 Alzheimer disease Diseases 0.000 claims description 3
• 208000001132 Osteoporosis Diseases 0.000 claims description 3
• 208000018737 Parkinson disease Diseases 0.000 claims description 3
• 208000006011 Stroke Diseases 0.000 claims description 3
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
• VDRMHRQQXLXAAC-UHFFFAOYSA-N [1-(4-hydroxycyclohexyl)-2-[[5-(2-methoxyphenyl)-1h-indazol-3-yl]amino]benzimidazol-5-yl]-pyrrolidin-1-ylmethanone Chemical compound COC1=CC=CC=C1C1=CC=C(NN=C2NC=3N(C4=CC=C(C=C4N=3)C(=O)N3CCCC3)C3CCC(O)CC3)C2=C1 VDRMHRQQXLXAAC-UHFFFAOYSA-N 0.000 claims description 3
• 230000001771 impaired effect Effects 0.000 claims description 3
• 206010028417 myasthenia gravis Diseases 0.000 claims description 3
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
• AXZVEOQAICRWJY-UHFFFAOYSA-N 1-(4-hydroxycyclohexyl)-2-[[5-(2-methoxyphenyl)-1h-indazol-3-yl]amino]-n-(3-methylbutyl)benzimidazole-5-carboxamide Chemical compound COC1=CC=CC=C1C1=CC=C(NN=C2NC=3N(C4=CC=C(C=C4N=3)C(=O)NCCC(C)C)C3CCC(O)CC3)C2=C1 AXZVEOQAICRWJY-UHFFFAOYSA-N 0.000 claims description 2
• QZMAOGLWCNTFCG-UHFFFAOYSA-N 1-(4-hydroxycyclohexyl)-n-(3-methylbutyl)-2-[[5-[2-(trifluoromethoxy)phenyl]-1h-indazol-3-yl]amino]benzimidazole-5-carboxamide Chemical compound N=1NC2=CC=C(C=3C(=CC=CC=3)OC(F)(F)F)C=C2C=1NC1=NC2=CC(C(=O)NCCC(C)C)=CC=C2N1C1CCC(O)CC1 QZMAOGLWCNTFCG-UHFFFAOYSA-N 0.000 claims description 2
• LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims description 2
• JIDRQSULGLZGQN-UHFFFAOYSA-N 3-[2-[(5-bromo-1h-indazol-3-yl)amino]benzimidazol-1-yl]propan-1-ol Chemical compound C1=CC=C2N(CCCO)C(NC=3C4=CC(Br)=CC=C4NN=3)=NC2=C1 JIDRQSULGLZGQN-UHFFFAOYSA-N 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• OYBSTTITNAOGPL-UHFFFAOYSA-N n-cyclopentyl-1-(4-hydroxycyclohexyl)-2-[[5-[2-(trifluoromethoxy)phenyl]-1h-indazol-3-yl]amino]benzimidazole-5-carboxamide Chemical compound C1CC(O)CCC1N1C2=CC=C(C(=O)NC3CCCC3)C=C2N=C1NC1=NNC2=CC=C(C=3C(=CC=CC=3)OC(F)(F)F)C=C12 OYBSTTITNAOGPL-UHFFFAOYSA-N 0.000 claims description 2
• 201000008482 osteoarthritis Diseases 0.000 claims description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
• 230000000694 effects Effects 0.000 abstract description 10
• 239000000126 substance Substances 0.000 abstract description 10
• 108010093036 interleukin receptors Proteins 0.000 abstract description 2
• 102000002467 interleukin receptors Human genes 0.000 abstract description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 2
• 150000002391 heterocyclic compounds Chemical class 0.000 abstract 2
• 150000003254 radicals Chemical class 0.000 description 130
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 119
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 112
• 239000000203 mixture Substances 0.000 description 107
• 125000003118 aryl group Chemical group 0.000 description 67
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 65
• 239000011541 reaction mixture Substances 0.000 description 60
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 55
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 39
• 235000019439 ethyl acetate Nutrition 0.000 description 38
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
• 125000001931 aliphatic group Chemical group 0.000 description 35
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 33
• 238000000034 method Methods 0.000 description 33
• 102100036342 Interleukin-1 receptor-associated kinase 1 Human genes 0.000 description 31
• 125000003368 amide group Chemical group 0.000 description 30
• 239000000243 solution Substances 0.000 description 30
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 29
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
• 101710199015 Interleukin-1 receptor-associated kinase 1 Proteins 0.000 description 27
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 26
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 26
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 25
• 239000000047 product Substances 0.000 description 24
• 229920000642 polymer Polymers 0.000 description 22
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 22
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 22
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
• 239000003814 drug Substances 0.000 description 20
• 239000012267 brine Substances 0.000 description 19
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
• 238000005481 NMR spectroscopy Methods 0.000 description 18
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-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
• 125000003342 alkenyl group Chemical group 0.000 description 18
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 18
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
• 229940124597 therapeutic agent Drugs 0.000 description 18
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• 239000007787 solid Substances 0.000 description 17
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 16
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 16
• 238000003756 stirring Methods 0.000 description 16
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
• 125000000304 alkynyl group Chemical group 0.000 description 15
• 125000004093 cyano group Chemical group *C#N 0.000 description 15
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• 229910052938 sodium sulfate Inorganic materials 0.000 description 15
• 235000011152 sodium sulphate Nutrition 0.000 description 15
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• 125000002619 bicyclic group Chemical group 0.000 description 14
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
• 235000019341 magnesium sulphate Nutrition 0.000 description 14
• 239000012074 organic phase Substances 0.000 description 14
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
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• 125000003435 aroyl group Chemical group 0.000 description 13
• 125000004429 atom Chemical group 0.000 description 13
• 238000006243 chemical reaction Methods 0.000 description 13
• 238000003818 flash chromatography Methods 0.000 description 13
• 239000001257 hydrogen Substances 0.000 description 13
• 150000003839 salts Chemical class 0.000 description 13
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• 150000003456 sulfonamides Chemical class 0.000 description 13
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 13
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 13
• 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 description 12
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
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• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 12
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 11
• 125000004104 aryloxy group Chemical group 0.000 description 11
• 239000004202 carbamide Substances 0.000 description 11
• 125000001188 haloalkyl group Chemical group 0.000 description 11
• 125000005553 heteroaryloxy group Chemical group 0.000 description 11
• 238000004128 high performance liquid chromatography Methods 0.000 description 11
• 125000004043 oxo group Chemical group O=* 0.000 description 11
• 238000002953 preparative HPLC Methods 0.000 description 11
• NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 11
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 11
• 239000013543 active substance Substances 0.000 description 10
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• 239000003795 chemical substances by application Substances 0.000 description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
• RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
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• 125000003107 substituted aryl group Chemical group 0.000 description 9
• 238000011282 treatment Methods 0.000 description 9
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 8
• KZCIYZXJEMGNJQ-UHFFFAOYSA-N 2-[(5-bromo-3-iodoindazol-1-yl)methoxy]ethyl-trimethylsilane Chemical compound BrC1=CC=C2N(COCC[Si](C)(C)C)N=C(I)C2=C1 KZCIYZXJEMGNJQ-UHFFFAOYSA-N 0.000 description 8
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 8
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• 229910002027 silica gel Inorganic materials 0.000 description 8
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• 210000004027 cell Anatomy 0.000 description 7
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 7
• 238000001514 detection method Methods 0.000 description 7
• 239000003480 eluent Substances 0.000 description 7
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• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
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• 125000004448 alkyl carbonyl group Chemical group 0.000 description 6
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• 125000002102 aryl alkyloxo group Chemical group 0.000 description 6
• 125000005605 benzo group Chemical group 0.000 description 6
• 238000004587 chromatography analysis Methods 0.000 description 6
• 125000004966 cyanoalkyl group Chemical group 0.000 description 6
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 6
• 125000002541 furyl group Chemical group 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
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• 229910000160 potassium phosphate Inorganic materials 0.000 description 6
• 235000011009 potassium phosphates Nutrition 0.000 description 6
• 238000010992 reflux Methods 0.000 description 6
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