SK287238B6 - Amidové deriváty, spôsob ich prípravy, farmaceutická kompozícia, ktorá ich obsahuje, a ich použitie - Google Patents

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Publication number

SK287238B6

SK287238B6 SK1311-2001A SK13112001A SK287238B6 SK 287238 B6 SK287238 B6 SK 287238B6 SK 13112001 A SK13112001 A SK 13112001A SK 287238 B6 SK287238 B6 SK 287238B6

Authority

SK

Slovakia

Prior art keywords

carbon atoms

alkyl

group

moiety

alkoxy

Prior art date

1999-03-17

Links

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• 150000001408 amides Chemical class 0.000 title claims abstract description 73
• 238000000034 method Methods 0.000 title claims abstract description 45
• 230000008569 process Effects 0.000 title claims abstract description 7
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 6
• 150000001875 compounds Chemical class 0.000 title claims description 131
• -1 cyano, mercapto, nitro, amino, carboxy Chemical group 0.000 claims abstract description 910
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 692
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 146
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 56
• 150000003839 salts Chemical class 0.000 claims abstract description 56
• 150000002148 esters Chemical class 0.000 claims abstract description 54
• 239000001257 hydrogen Substances 0.000 claims abstract description 40
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 40
• 125000003118 aryl group Chemical group 0.000 claims abstract description 39
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 31
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 27
• 201000010099 disease Diseases 0.000 claims abstract description 24
• 238000002360 preparation method Methods 0.000 claims abstract description 24
• 102000004127 Cytokines Human genes 0.000 claims abstract description 23
• 108090000695 Cytokines Proteins 0.000 claims abstract description 23
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 21
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 19
• 238000011282 treatment Methods 0.000 claims abstract description 16
• 125000001769 aryl amino group Chemical group 0.000 claims abstract description 14
• 125000004104 aryloxy group Chemical group 0.000 claims abstract description 14
• 125000005843 halogen group Chemical group 0.000 claims abstract description 12
• 230000001404 mediated effect Effects 0.000 claims abstract description 12
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 9
• 125000004432 carbon atom Chemical group C* 0.000 claims description 844
• 125000001424 substituent group Chemical group 0.000 claims description 114
• 125000001589 carboacyl group Chemical group 0.000 claims description 73
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 71
• 229910052757 nitrogen Inorganic materials 0.000 claims description 70
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 59
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 59
• 125000000623 heterocyclic group Chemical group 0.000 claims description 55
• 229910052799 carbon Inorganic materials 0.000 claims description 53
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
• 125000001072 heteroaryl group Chemical group 0.000 claims description 46
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 45
• 238000001727 in vivo Methods 0.000 claims description 38
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 30
• 229910052736 halogen Inorganic materials 0.000 claims description 30
• 150000002367 halogens Chemical class 0.000 claims description 27
• 125000005122 aminoalkylamino group Chemical group 0.000 claims description 25
• SSSDCHOJYWJLKM-UHFFFAOYSA-N 4-methyl-n-[4-methyl-3-(2-methyl-4-oxoquinazolin-3-yl)phenyl]benzamide Chemical compound C1=CC(C)=CC=C1C(=O)NC1=CC=C(C)C(N2C(C3=CC=CC=C3N=C2C)=O)=C1 SSSDCHOJYWJLKM-UHFFFAOYSA-N 0.000 claims description 23
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 23
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
• BGASEZKJFFGWSB-UHFFFAOYSA-N 4-methoxy-n-[4-methyl-3-(2-methyl-4-oxoquinazolin-3-yl)phenyl]benzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=CC=C(C)C(N2C(C3=CC=CC=C3N=C2C)=O)=C1 BGASEZKJFFGWSB-UHFFFAOYSA-N 0.000 claims description 21
• 239000002253 acid Substances 0.000 claims description 21
• HRGRYWJTIGGDTB-UHFFFAOYSA-N n-[4-methyl-3-(2-methyl-4-oxoquinazolin-3-yl)phenyl]benzamide Chemical compound C1=C(N2C(C3=CC=CC=C3N=C2C)=O)C(C)=CC=C1NC(=O)C1=CC=CC=C1 HRGRYWJTIGGDTB-UHFFFAOYSA-N 0.000 claims description 21
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
• 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 19
• 125000006239 protecting group Chemical group 0.000 claims description 18
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 18
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 17
• 125000002431 aminoalkoxy group Chemical group 0.000 claims description 17
• 229910052731 fluorine Inorganic materials 0.000 claims description 17
• 125000004076 pyridyl group Chemical group 0.000 claims description 17
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 16
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 16
• 229910052801 chlorine Inorganic materials 0.000 claims description 16
• 238000004519 manufacturing process Methods 0.000 claims description 16
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 15
• 150000001721 carbon Chemical group 0.000 claims description 15
• 229920006395 saturated elastomer Polymers 0.000 claims description 15
• 125000001153 fluoro group Chemical group F* 0.000 claims description 14
• 125000001544 thienyl group Chemical group 0.000 claims description 14
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 13
• 125000003277 amino group Chemical group 0.000 claims description 13
• 125000005239 aroylamino group Chemical group 0.000 claims description 13
• 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 13
• 125000004429 atom Chemical group 0.000 claims description 13
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 13
• 239000000460 chlorine Substances 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 13
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 12
• 239000011737 fluorine Substances 0.000 claims description 12
• 125000002541 furyl group Chemical group 0.000 claims description 12
• 125000005224 heteroarylcarbonylamino group Chemical group 0.000 claims description 12
• 125000005419 heteroarylsulfonylamino group Chemical group 0.000 claims description 12
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 11
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 11
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 11
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
• 125000005242 carbamoyl alkyl group Chemical group 0.000 claims description 11
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 11
• 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims description 11
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
• 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 10
• 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 10
• 125000003282 alkyl amino group Chemical group 0.000 claims description 10
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 10
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
• 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 10
• 125000005842 heteroatom Chemical group 0.000 claims description 10
• 239000001301 oxygen Substances 0.000 claims description 10
• 229910052760 oxygen Inorganic materials 0.000 claims description 10
• 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 10
• 239000011593 sulfur Chemical group 0.000 claims description 10
• 229910052717 sulfur Chemical group 0.000 claims description 10
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 9
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 9
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
• 125000003342 alkenyl group Chemical group 0.000 claims description 9
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 9
• 125000005530 alkylenedioxy group Chemical group 0.000 claims description 9
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 9
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 9
• 125000000524 functional group Chemical group 0.000 claims description 9
• 125000005241 heteroarylamino group Chemical group 0.000 claims description 9
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 9
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 9
• 125000003386 piperidinyl group Chemical group 0.000 claims description 9
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
• 125000005085 alkoxycarbonylalkoxy group Chemical group 0.000 claims description 8
• 125000003418 alkyl amino alkoxy group Chemical group 0.000 claims description 8
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
• 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 8
• 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 claims description 8
• 125000002619 bicyclic group Chemical group 0.000 claims description 8
• 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 8
• 125000002950 monocyclic group Chemical group 0.000 claims description 8
• 125000004193 piperazinyl group Chemical group 0.000 claims description 8
• 125000005493 quinolyl group Chemical group 0.000 claims description 8
• 125000000335 thiazolyl group Chemical group 0.000 claims description 8
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 7
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 7
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 7
• 125000005111 carboxyalkoxy group Chemical group 0.000 claims description 7
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 7
• 125000004992 haloalkylamino group Chemical group 0.000 claims description 7
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 7
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 7
• 125000002883 imidazolyl group Chemical group 0.000 claims description 7
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 7
• 125000001041 indolyl group Chemical group 0.000 claims description 7
• 125000005956 isoquinolyl group Chemical group 0.000 claims description 7
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 7
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 7
• 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 7
• 125000002971 oxazolyl group Chemical group 0.000 claims description 7
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 7
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 7
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 7
• 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 6
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
• 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 6
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 6
• 150000001412 amines Chemical class 0.000 claims description 6
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
• 229910052794 bromium Inorganic materials 0.000 claims description 6
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
• 125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 6
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
• 125000002757 morpholinyl group Chemical group 0.000 claims description 6
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical group C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 5
• 125000004423 acyloxy group Chemical group 0.000 claims description 5
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 5
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 5
• 125000005191 hydroxyalkylamino group Chemical group 0.000 claims description 5
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 5
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 5
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 4
• 125000004364 3-pyrrolinyl group Chemical group [H]C1=C([H])C([H])([H])N(*)C1([H])[H] 0.000 claims description 4
• 125000002252 acyl group Chemical group 0.000 claims description 4
• 125000000304 alkynyl group Chemical group 0.000 claims description 4
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 4
• 125000005159 cyanoalkoxy group Chemical group 0.000 claims description 4
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 4
• 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 claims description 4
• FDPVTENMNDHFNK-UHFFFAOYSA-N 2-amino-n-phenylbenzamide Chemical compound NC1=CC=CC=C1C(=O)NC1=CC=CC=C1 FDPVTENMNDHFNK-UHFFFAOYSA-N 0.000 claims description 3
• 238000010976 amide bond formation reaction Methods 0.000 claims description 3
• 125000002393 azetidinyl group Chemical group 0.000 claims description 3
• 125000001188 haloalkyl group Chemical group 0.000 claims description 3
• UICJDYQTBCEDQP-UHFFFAOYSA-N n-[4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3-yl]phenyl]dibenzofuran-4-carboxamide Chemical compound C1CN(C)CCN1C1=CC=C(N=CN(C=2C(=CC=C(NC(=O)C=3C=4OC5=CC=CC=C5C=4C=CC=3)C=2)C)C2=O)C2=C1 UICJDYQTBCEDQP-UHFFFAOYSA-N 0.000 claims description 3
• FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical group CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 claims description 2
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
• IVDMCFNZRMBUFA-UHFFFAOYSA-N 3-(furan-2-yl)-n-[4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3-yl]phenyl]benzamide Chemical compound C1CN(C)CCN1C1=CC=C(N=CN(C=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C=3OC=CC=3)C=2)C)C2=O)C2=C1 IVDMCFNZRMBUFA-UHFFFAOYSA-N 0.000 claims description 2
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
• CFAIZVNTSWWMFR-UHFFFAOYSA-N n-[3-[8-[3-(dimethylamino)propyl-methylamino]-4-oxoquinazolin-3-yl]-4-methylphenyl]-2-morpholin-4-ylpyridine-4-carboxamide Chemical compound CN(C)CCCN(C)C1=CC=CC(C2=O)=C1N=CN2C(C(=CC=1)C)=CC=1NC(=O)C(C=1)=CC=NC=1N1CCOCC1 CFAIZVNTSWWMFR-UHFFFAOYSA-N 0.000 claims description 2
• BLSPWFIREKMTOA-UHFFFAOYSA-N n-[4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3-yl]phenyl]-2-morpholin-4-ylpyridine-4-carboxamide Chemical compound C1CN(C)CCN1C1=CC=C(N=CN(C=2C(=CC=C(NC(=O)C=3C=C(N=CC=3)N3CCOCC3)C=2)C)C2=O)C2=C1 BLSPWFIREKMTOA-UHFFFAOYSA-N 0.000 claims description 2
• WQDXNLSFVMCBEV-UHFFFAOYSA-N n-[4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3-yl]phenyl]-2-piperidin-1-ylpyridine-4-carboxamide Chemical compound C1CN(C)CCN1C1=CC=C(N=CN(C=2C(=CC=C(NC(=O)C=3C=C(N=CC=3)N3CCCCC3)C=2)C)C2=O)C2=C1 WQDXNLSFVMCBEV-UHFFFAOYSA-N 0.000 claims description 2
• 125000001624 naphthyl group Chemical group 0.000 claims description 2
• XHPVOSNOIWGRQQ-UHFFFAOYSA-N 4-pyridin-2-ylmorpholine Chemical compound C1COCCN1C1=CC=CC=N1 XHPVOSNOIWGRQQ-UHFFFAOYSA-N 0.000 claims 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
• 125000006524 alkoxy alkyl amino group Chemical group 0.000 claims 1
• 125000005084 alkoxyalkylaminoalkyl group Chemical group 0.000 claims 1
• 125000005055 alkyl alkoxy group Chemical group 0.000 claims 1
• 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims 1
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical group [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 1
• 125000004947 alkyl aryl amino group Chemical group 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 207
• 239000000203 mixture Substances 0.000 description 181
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 150
• 238000001819 mass spectrum Methods 0.000 description 145
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 142
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 97
• 239000000047 product Substances 0.000 description 74
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 73
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 60
• 239000007858 starting material Substances 0.000 description 57
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 49
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
• 239000000243 solution Substances 0.000 description 45
• 239000000463 material Substances 0.000 description 42
• 239000007787 solid Substances 0.000 description 36
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 32
• 239000012258 stirred mixture Substances 0.000 description 30
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
• 238000006243 chemical reaction Methods 0.000 description 28
• 239000011541 reaction mixture Substances 0.000 description 27
• 239000000706 filtrate Substances 0.000 description 25
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 24
• 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 24
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 23
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 23
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 22
• 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 22
• 102100040247 Tumor necrosis factor Human genes 0.000 description 21
• 239000002244 precipitate Substances 0.000 description 21
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 18
• 239000003054 catalyst Substances 0.000 description 18
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
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