JP5868996B2 - ＩＩＩ型受容体チロシンキナーゼ阻害剤としての置換Ｎ−（１Ｈ−インダゾール−４−イル）イミダゾ［１，２−ａ］ピリジン−３−カルボキサミド化合物 - Google Patents

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Publication number

JP5868996B2

JP5868996B2 JP2013544674A JP2013544674A JP5868996B2 JP 5868996 B2 JP5868996 B2 JP 5868996B2 JP 2013544674 A JP2013544674 A JP 2013544674A JP 2013544674 A JP2013544674 A JP 2013544674A JP 5868996 B2 JP5868996 B2 JP 5868996B2

Authority

JP

Japan

Prior art keywords

alkyl

methyl

compound

alkoxy

hetcyc

Prior art date

2010-12-13

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

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• AYAOSDNSSUARDZ-UHFFFAOYSA-N n-(1h-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide Chemical class C1=CC=CN2C(C(NC=3C=4C=NNC=4C=CC=3)=O)=CN=C21 AYAOSDNSSUARDZ-UHFFFAOYSA-N 0.000 title description 3
• 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 414
• 125000000217 alkyl group Chemical group 0.000 claims description 366
• 125000003545 alkoxy group Chemical group 0.000 claims description 244
• 239000000203 mixture Substances 0.000 claims description 238
• -1 pyridinonyl Chemical group 0.000 claims description 209
• 150000003839 salts Chemical class 0.000 claims description 109
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 104
• 125000001424 substituent group Chemical group 0.000 claims description 87
• 238000000034 method Methods 0.000 claims description 86
• 201000010099 disease Diseases 0.000 claims description 79
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 77
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 65
• 206010028980 Neoplasm Diseases 0.000 claims description 54
• 238000011282 treatment Methods 0.000 claims description 53
• 229920006395 saturated elastomer Polymers 0.000 claims description 46
• 239000002585 base Substances 0.000 claims description 43
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 42
• 125000005842 heteroatom Chemical group 0.000 claims description 42
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 42
• 201000011510 cancer Diseases 0.000 claims description 41
• 210000000988 bone and bone Anatomy 0.000 claims description 40
• 206010016654 Fibrosis Diseases 0.000 claims description 36
• 241000124008 Mammalia Species 0.000 claims description 36
• 230000004761 fibrosis Effects 0.000 claims description 34
• 150000002367 halogens Chemical class 0.000 claims description 34
• 208000002193 Pain Diseases 0.000 claims description 33
• 229910052736 halogen Inorganic materials 0.000 claims description 33
• 229910052757 nitrogen Inorganic materials 0.000 claims description 32
• 229910052739 hydrogen Inorganic materials 0.000 claims description 31
• 229910052731 fluorine Inorganic materials 0.000 claims description 30
• 208000027866 inflammatory disease Diseases 0.000 claims description 28
• 208000023275 Autoimmune disease Diseases 0.000 claims description 27
• 229910052801 chlorine Inorganic materials 0.000 claims description 27
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 26
• 230000008878 coupling Effects 0.000 claims description 25
• 238000010168 coupling process Methods 0.000 claims description 25
• 238000005859 coupling reaction Methods 0.000 claims description 25
• 208000035475 disorder Diseases 0.000 claims description 24
• 125000000623 heterocyclic group Chemical group 0.000 claims description 23
• 238000004519 manufacturing process Methods 0.000 claims description 21
• 230000008569 process Effects 0.000 claims description 20
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 17
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 16
• 125000001072 heteroaryl group Chemical group 0.000 claims description 15
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
• 229910052763 palladium Inorganic materials 0.000 claims description 14
• 239000003054 catalyst Substances 0.000 claims description 13
• 239000003153 chemical reaction reagent Substances 0.000 claims description 13
• 229910052717 sulfur Inorganic materials 0.000 claims description 13
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 12
• 125000004429 atom Chemical group 0.000 claims description 12
• 239000003638 chemical reducing agent Substances 0.000 claims description 11
• 239000003446 ligand Substances 0.000 claims description 11
• 229910052794 bromium Inorganic materials 0.000 claims description 10
• 125000006239 protecting group Chemical group 0.000 claims description 10
• 210000001519 tissue Anatomy 0.000 claims description 9
• 238000002560 therapeutic procedure Methods 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• 206010027476 Metastases Diseases 0.000 claims description 6
• 239000002253 acid Substances 0.000 claims description 6
• 230000015572 biosynthetic process Effects 0.000 claims description 6
• 239000003085 diluting agent Substances 0.000 claims description 6
• 230000009401 metastasis Effects 0.000 claims description 6
• 206010051066 Gastrointestinal stromal tumour Diseases 0.000 claims description 5
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 5
• 125000002619 bicyclic group Chemical group 0.000 claims description 5
• 150000001723 carbon free-radicals Chemical class 0.000 claims description 5
• 201000011243 gastrointestinal stromal tumor Diseases 0.000 claims description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
• 239000007800 oxidant agent Substances 0.000 claims description 4
• 150000003254 radicals Chemical class 0.000 claims description 4
• 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 claims description 4
• JUQWFONZRDXAAB-UHFFFAOYSA-N 1-methyl-1-oxidopiperazin-1-ium Chemical compound C[N+]1([O-])CCNCC1 JUQWFONZRDXAAB-UHFFFAOYSA-N 0.000 claims description 3
• 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 3
• 206010028537 myelofibrosis Diseases 0.000 claims description 3
• 238000006467 substitution reaction Methods 0.000 claims description 3
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 2
• 206010006187 Breast cancer Diseases 0.000 claims description 2
• 208000026310 Breast neoplasm Diseases 0.000 claims description 2
• 208000007569 Giant Cell Tumors Diseases 0.000 claims description 2
• 201000010915 Glioblastoma multiforme Diseases 0.000 claims description 2
• 208000034578 Multiple myelomas Diseases 0.000 claims description 2
• 206010033128 Ovarian cancer Diseases 0.000 claims description 2
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
• 206010060862 Prostate cancer Diseases 0.000 claims description 2
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
• 208000005017 glioblastoma Diseases 0.000 claims description 2
• 201000001441 melanoma Diseases 0.000 claims description 2
• 201000004595 synovitis Diseases 0.000 claims description 2
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims 2
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 1
• 201000011143 bone giant cell tumor Diseases 0.000 claims 1
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
• 210000002435 tendon Anatomy 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 296
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 283
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 186
• 238000002360 preparation method Methods 0.000 description 183
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 146
• 235000019439 ethyl acetate Nutrition 0.000 description 125
• 239000007787 solid Substances 0.000 description 120
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 114
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 105
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 92
• 239000000243 solution Substances 0.000 description 91
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 79
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 77
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 76
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 73
• 238000006243 chemical reaction Methods 0.000 description 63
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 62
• 206010012812 Diffuse cutaneous mastocytosis Diseases 0.000 description 61
• 239000011541 reaction mixture Substances 0.000 description 61
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 55
• 239000000047 product Substances 0.000 description 51
• 230000002829 reductive effect Effects 0.000 description 51
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 50
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 47
• 229910052938 sodium sulfate Inorganic materials 0.000 description 41
• 235000011152 sodium sulphate Nutrition 0.000 description 41
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
• 239000000284 extract Substances 0.000 description 39
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 36
• 235000005152 nicotinamide Nutrition 0.000 description 36
• 239000011570 nicotinamide Substances 0.000 description 36
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 35
• 239000012267 brine Substances 0.000 description 35
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 35
• 238000003756 stirring Methods 0.000 description 31
• 210000004027 cell Anatomy 0.000 description 30
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
• 238000004440 column chromatography Methods 0.000 description 28
• 239000000377 silicon dioxide Substances 0.000 description 28
• 239000012043 crude product Substances 0.000 description 27
• 239000011734 sodium Substances 0.000 description 27
• 239000002904 solvent Substances 0.000 description 26
• 239000000706 filtrate Substances 0.000 description 25
• 239000003112 inhibitor Substances 0.000 description 25
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• ZMBYQTGAXZOMOO-UHFFFAOYSA-N imidazo[1,2-a]pyridine-3-carboxamide Chemical compound C1=CC=CN2C(C(=O)N)=CN=C21 ZMBYQTGAXZOMOO-UHFFFAOYSA-N 0.000 description 24
• 239000000463 material Substances 0.000 description 24
• 125000004432 carbon atom Chemical group C* 0.000 description 22
• 210000002540 macrophage Anatomy 0.000 description 21
• 239000000725 suspension Substances 0.000 description 21
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 20
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 20
• 239000012299 nitrogen atmosphere Substances 0.000 description 20
• 238000012746 preparative thin layer chromatography Methods 0.000 description 20
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 19
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 19
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 239000013058 crude material Substances 0.000 description 18
• 239000003480 eluent Substances 0.000 description 18
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
• KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 17
• 239000012071 phase Substances 0.000 description 17
• 239000002244 precipitate Substances 0.000 description 17
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
• 239000010410 layer Substances 0.000 description 16
• 239000012044 organic layer Substances 0.000 description 16
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
• 229910000027 potassium carbonate Inorganic materials 0.000 description 15
• 235000011181 potassium carbonates Nutrition 0.000 description 15
• 238000001914 filtration Methods 0.000 description 14
• 239000003921 oil Substances 0.000 description 14
• 235000019198 oils Nutrition 0.000 description 14
• 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 13
• 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 13
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 13
• 239000005457 ice water Substances 0.000 description 13
• 238000010992 reflux Methods 0.000 description 13
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
• 235000017557 sodium bicarbonate Nutrition 0.000 description 13
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 12
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
• 208000003076 Osteolysis Diseases 0.000 description 11
• 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 11
• 229910052799 carbon Inorganic materials 0.000 description 11
• 208000029791 lytic metastatic bone lesion Diseases 0.000 description 11
• 210000002997 osteoclast Anatomy 0.000 description 11
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
• 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 10
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
• 239000000010 aprotic solvent Substances 0.000 description 10
• 239000008346 aqueous phase Substances 0.000 description 10
• 150000002170 ethers Chemical class 0.000 description 10
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 10
• PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 10
• 210000001616 monocyte Anatomy 0.000 description 10
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
• 229910052760 oxygen Inorganic materials 0.000 description 10
• 239000000126 substance Substances 0.000 description 10
• WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 9
• FPEYDBWXOQJGJH-UHFFFAOYSA-N 3-methyl-1-[(6-methylpyridin-2-yl)methyl]indazol-4-amine Chemical compound C12=CC=CC(N)=C2C(C)=NN1CC1=CC=CC(C)=N1 FPEYDBWXOQJGJH-UHFFFAOYSA-N 0.000 description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• 125000004414 alkyl thio group Chemical group 0.000 description 9
• 238000003556 assay Methods 0.000 description 9
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 9
• 229910000024 caesium carbonate Inorganic materials 0.000 description 9
• 239000003814 drug Substances 0.000 description 9
• 125000001153 fluoro group Chemical group F* 0.000 description 9
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 9
• 229910017051 nitrogen difluoride Inorganic materials 0.000 description 9
• 239000012074 organic phase Substances 0.000 description 9
• 238000011160 research Methods 0.000 description 9
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 9
• 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 8
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
• DWXKSCKBUSAOKS-UHFFFAOYSA-N ethyl 2-chloro-3-oxopropanoate Chemical compound CCOC(=O)C(Cl)C=O DWXKSCKBUSAOKS-UHFFFAOYSA-N 0.000 description 8
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 8
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 8
• 125000006413 ring segment Chemical group 0.000 description 8
• 238000000926 separation method Methods 0.000 description 8
• 239000000741 silica gel Substances 0.000 description 8
• 229910002027 silica gel Inorganic materials 0.000 description 8
• 229910000029 sodium carbonate Inorganic materials 0.000 description 8
• 235000017550 sodium carbonate Nutrition 0.000 description 8
• NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 description 7
• AOTAXYVEONHYHY-UHFFFAOYSA-N 3-iodo-4-nitro-2h-indazole Chemical compound [O-][N+](=O)C1=CC=CC2=C1C(I)=NN2 AOTAXYVEONHYHY-UHFFFAOYSA-N 0.000 description 7
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
• 241000282412 Homo Species 0.000 description 7
• 208000028389 Nerve injury Diseases 0.000 description 7
• 150000001721 carbon Chemical group 0.000 description 7
• YJISWZLKSURKFM-UHFFFAOYSA-N ethyl 7-fluoroimidazo[1,2-a]pyridine-3-carboxylate Chemical compound C1=C(F)C=CN2C(C(=O)OCC)=CN=C21 YJISWZLKSURKFM-UHFFFAOYSA-N 0.000 description 7
• 239000001257 hydrogen Substances 0.000 description 7
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 7
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
• 230000008764 nerve damage Effects 0.000 description 7
• 125000003386 piperidinyl group Chemical group 0.000 description 7
• 238000000746 purification Methods 0.000 description 7
• XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 6
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 6
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 6
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