SG181861A1 - Substituted n-(1h-indazol-4-yl)imidazo[1, 2-a]pyridine-3- carboxamide compounds as cfms inhibitors - Google Patents

Info

Publication number

SG181861A1

SG181861A1 SG2012046009A SG2012046009A SG181861A1 SG 181861 A1 SG181861 A1 SG 181861A1 SG 2012046009 A SG2012046009 A SG 2012046009A SG 2012046009 A SG2012046009 A SG 2012046009A SG 181861 A1 SG181861 A1 SG 181861A1

Authority

SG

Singapore

Prior art keywords

alkyl

hetcyc

alkoxy

formula

compound

Prior art date

2009-12-21

Links

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• 239000003112 inhibitor Substances 0.000 title abstract description 23
• 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
• 150000001875 compounds Chemical class 0.000 claims abstract description 288
• 238000011282 treatment Methods 0.000 claims abstract description 45
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 40
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 39
• 210000000988 bone and bone Anatomy 0.000 claims abstract description 34
• 150000003839 salts Chemical class 0.000 claims abstract description 33
• 201000010099 disease Diseases 0.000 claims abstract description 30
• 201000011510 cancer Diseases 0.000 claims abstract description 25
• 208000002193 Pain Diseases 0.000 claims abstract description 22
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 17
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 16
• 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 16
• 125000000217 alkyl group Chemical group 0.000 claims description 316
• 125000003545 alkoxy group Chemical group 0.000 claims description 266
• 238000002360 preparation method Methods 0.000 claims description 149
• 125000001424 substituent group Chemical group 0.000 claims description 106
• -1 hetCyc'’- Chemical group 0.000 claims description 87
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 83
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 69
• 229910052757 nitrogen Inorganic materials 0.000 claims description 59
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 54
• 229910052739 hydrogen Inorganic materials 0.000 claims description 52
• 239000002585 base Substances 0.000 claims description 49
• 238000000034 method Methods 0.000 claims description 46
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 46
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 43
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 41
• 229910052760 oxygen Inorganic materials 0.000 claims description 35
• 125000005842 heteroatom Chemical group 0.000 claims description 33
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 32
• 230000008878 coupling Effects 0.000 claims description 31
• 238000010168 coupling process Methods 0.000 claims description 31
• 238000005859 coupling reaction Methods 0.000 claims description 31
• 229910052736 halogen Inorganic materials 0.000 claims description 31
• 150000002367 halogens Chemical class 0.000 claims description 27
• 125000000623 heterocyclic group Chemical group 0.000 claims description 26
• 229910052763 palladium Inorganic materials 0.000 claims description 25
• 125000004076 pyridyl group Chemical group 0.000 claims description 24
• 229920006395 saturated elastomer Polymers 0.000 claims description 22
• 241000124008 Mammalia Species 0.000 claims description 20
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 20
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 20
• 125000004429 atom Chemical group 0.000 claims description 19
• 239000003054 catalyst Substances 0.000 claims description 19
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
• 229910052794 bromium Inorganic materials 0.000 claims description 16
• 229910052717 sulfur Inorganic materials 0.000 claims description 16
• IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate Chemical compound [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 claims description 15
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 15
• 229910052731 fluorine Inorganic materials 0.000 claims description 14
• 229910052740 iodine Inorganic materials 0.000 claims description 14
• PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 claims description 14
• 229910017051 nitrogen difluoride Inorganic materials 0.000 claims description 14
• 239000003153 chemical reaction reagent Substances 0.000 claims description 12
• 229910052799 carbon Inorganic materials 0.000 claims description 11
• 239000003638 chemical reducing agent Substances 0.000 claims description 11
• 239000003446 ligand Substances 0.000 claims description 11
• 125000004414 alkyl thio group Chemical group 0.000 claims description 10
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 10
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 10
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 9
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 8
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
• 229910052801 chlorine Inorganic materials 0.000 claims description 8
• 230000008569 process Effects 0.000 claims description 8
• 125000006413 ring segment Chemical group 0.000 claims description 8
• 238000002560 therapeutic procedure Methods 0.000 claims description 8
• PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 claims description 8
• 125000006239 protecting group Chemical group 0.000 claims description 7
• 150000003254 radicals Chemical class 0.000 claims description 7
• 125000004990 dihydroxyalkyl group Chemical group 0.000 claims description 6
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 6
• 125000001072 heteroaryl group Chemical group 0.000 claims description 6
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
• 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 6
• 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
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 230000009467 reduction Effects 0.000 claims description 5
• NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 claims description 4
• 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 4
• 239000002253 acid Substances 0.000 claims description 4
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 4
• 150000001723 carbon free-radicals Chemical class 0.000 claims description 4
• 239000003795 chemical substances by application Substances 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 230000003213 activating effect Effects 0.000 claims description 3
• 239000007822 coupling agent Substances 0.000 claims description 3
• 239000007800 oxidant agent Substances 0.000 claims description 3
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
• 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 claims description 2
• JUQWFONZRDXAAB-UHFFFAOYSA-N 1-methyl-1-oxidopiperazin-1-ium Chemical compound C[N+]1([O-])CCNCC1 JUQWFONZRDXAAB-UHFFFAOYSA-N 0.000 claims description 2
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 2
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
• 150000002831 nitrogen free-radicals Chemical group 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 439
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 365
• 239000000203 mixture Substances 0.000 description 243
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 236
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 201
• 239000000243 solution Substances 0.000 description 140
• 230000002829 reductive effect Effects 0.000 description 138
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 134
• 239000011541 reaction mixture Substances 0.000 description 129
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 100
• 239000000047 product Substances 0.000 description 96
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 95
• 235000019439 ethyl acetate Nutrition 0.000 description 93
• 239000007787 solid Substances 0.000 description 79
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 76
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 67
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 66
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 61
• 238000006243 chemical reaction Methods 0.000 description 60
• 238000010898 silica gel chromatography Methods 0.000 description 60
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 55
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 49
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 48
• 239000002904 solvent Substances 0.000 description 46
• 239000001257 hydrogen Substances 0.000 description 44
• 239000000463 material Substances 0.000 description 44
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 41
• 235000011114 ammonium hydroxide Nutrition 0.000 description 41
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 40
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
• 239000012467 final product Substances 0.000 description 35
• 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 33
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 31
• 235000005152 nicotinamide Nutrition 0.000 description 31
• 239000011570 nicotinamide Substances 0.000 description 31
• DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 31
• STWNGMSGPBZFMX-UHFFFAOYSA-N pyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=C1.NC(=O)C1=CC=CN=C1 STWNGMSGPBZFMX-UHFFFAOYSA-N 0.000 description 31
• 239000000377 silicon dioxide Substances 0.000 description 30
• 239000007864 aqueous solution Substances 0.000 description 29
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 28
• 239000012074 organic phase Substances 0.000 description 28
• 238000001914 filtration Methods 0.000 description 27
• 125000004432 carbon atom Chemical group C* 0.000 description 25
• 210000004027 cell Anatomy 0.000 description 25
• 238000003756 stirring Methods 0.000 description 25
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
• 238000012746 preparative thin layer chromatography Methods 0.000 description 22
• 239000012071 phase Substances 0.000 description 21
• 229910052938 sodium sulfate Inorganic materials 0.000 description 21
• 235000011152 sodium sulphate Nutrition 0.000 description 21
• 239000000725 suspension Substances 0.000 description 21
• 239000000706 filtrate Substances 0.000 description 20
• 210000002540 macrophage Anatomy 0.000 description 20
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
• 239000011734 sodium Substances 0.000 description 19
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
• 239000012267 brine Substances 0.000 description 18
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
• 239000012298 atmosphere Substances 0.000 description 17
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
• 239000000908 ammonium hydroxide Substances 0.000 description 16
• 239000012043 crude product Substances 0.000 description 16
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 16
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 16
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 16
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
• 238000000746 purification Methods 0.000 description 15
• 208000003076 Osteolysis Diseases 0.000 description 14
• 239000000010 aprotic solvent Substances 0.000 description 14
• 239000008346 aqueous phase Substances 0.000 description 14
• 208000029791 lytic metastatic bone lesion Diseases 0.000 description 14
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 14
• 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 14
• 150000002170 ethers Chemical class 0.000 description 13
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 12
• 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 12
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 12
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 12
• 239000003921 oil Substances 0.000 description 12
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 11
• 125000001153 fluoro group Chemical group F* 0.000 description 11
• 210000002997 osteoclast Anatomy 0.000 description 11
• 125000003386 piperidinyl group Chemical group 0.000 description 11
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
• 238000003556 assay Methods 0.000 description 10
• 229910000024 caesium carbonate Inorganic materials 0.000 description 10
• 239000000284 extract Substances 0.000 description 10
• 125000004193 piperazinyl group Chemical group 0.000 description 10
• 229910000027 potassium carbonate Inorganic materials 0.000 description 10
• 235000011181 potassium carbonates Nutrition 0.000 description 10
• 238000005406 washing Methods 0.000 description 10
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
• 241001465754 Metazoa Species 0.000 description 9
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
• 208000035475 disorder Diseases 0.000 description 9
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 9
• 239000000741 silica gel Substances 0.000 description 9
• 229910002027 silica gel Inorganic materials 0.000 description 9
• 229960001866 silicon dioxide Drugs 0.000 description 9
• 239000002002 slurry Substances 0.000 description 9
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
• 208000028389 Nerve injury Diseases 0.000 description 8
• 229910000288 alkali metal carbonate Inorganic materials 0.000 description 8
• 229910052786 argon Inorganic materials 0.000 description 8
• 229910002091 carbon monoxide Inorganic materials 0.000 description 8
• 239000000543 intermediate Substances 0.000 description 8
• 239000012280 lithium aluminium hydride Substances 0.000 description 8
• 230000008764 nerve damage Effects 0.000 description 8
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
• 238000010992 reflux Methods 0.000 description 8
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 8
• 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
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
• 125000002393 azetidinyl group Chemical group 0.000 description 7
• 238000004440 column chromatography Methods 0.000 description 7
• SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 7
• 239000003814 drug Substances 0.000 description 7
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
• 229910052744 lithium Inorganic materials 0.000 description 7
• 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 7
• 238000003760 magnetic stirring Methods 0.000 description 7
• 210000001616 monocyte Anatomy 0.000 description 7
• 125000002757 morpholinyl group Chemical group 0.000 description 7
• LQXXSGZJEBRDNS-UHFFFAOYSA-N n-[3-ethyl-1-[(6-oxo-1h-pyridin-2-yl)methyl]indazol-4-yl]imidazo[1,2-a]pyridine-3-carboxamide Chemical compound C12=CC=CC(NC(=O)C=3N4C=CC=CC4=NC=3)=C2C(CC)=NN1CC1=CC=CC(O)=N1 LQXXSGZJEBRDNS-UHFFFAOYSA-N 0.000 description 7
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
• 235000017557 sodium bicarbonate Nutrition 0.000 description 7
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
• 229910000104 sodium hydride Inorganic materials 0.000 description 7
• RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 7
• PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
• WJFDCFHWFHCLIW-UHFFFAOYSA-N 2-(bromomethyl)-6-methylpyridine Chemical compound CC1=CC=CC(CBr)=N1 WJFDCFHWFHCLIW-UHFFFAOYSA-N 0.000 description 6
• PWSHDKJRJTWMGD-UHFFFAOYSA-N 3-iodo-1-[(6-methylpyridin-2-yl)methyl]-4-nitroindazole Chemical compound CC1=CC=CC(CN2C3=CC=CC(=C3C(I)=N2)[N+]([O-])=O)=N1 PWSHDKJRJTWMGD-UHFFFAOYSA-N 0.000 description 6
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