BRPI0809088A2 - Pirimidodiazepinas substituídas úteis como inibidoras de plk1 - Google Patents

Info

Publication number

BRPI0809088A2

BRPI0809088A2 BRPI0809088-2A BRPI0809088A BRPI0809088A2 BR PI0809088 A2 BRPI0809088 A2 BR PI0809088A2 BR PI0809088 A BRPI0809088 A BR PI0809088A BR PI0809088 A2 BRPI0809088 A2 BR PI0809088A2

Authority

BR

Brazil

Prior art keywords

methyl

mol

tetrahydro

diazepin

cyclopentyl

Prior art date

2007-03-22

Links

• Espacenet
• Global Dossier
• Discuss

• 102100031463 Serine/threonine-protein kinase PLK1 Human genes 0.000 title description 14
• 108010056274 polo-like kinase 1 Proteins 0.000 title description 13
• 239000003112 inhibitor Substances 0.000 title description 4
• OHXQYFCNXHGKPJ-UHFFFAOYSA-N 1h-pyrimido[5,4-c]diazepine Chemical class N1N=CC=CC2=NC=NC=C12 OHXQYFCNXHGKPJ-UHFFFAOYSA-N 0.000 title 1
• 239000000203 mixture Substances 0.000 claims description 396
• -1 N-benzyl piperidinyl Chemical group 0.000 claims description 361
• 150000001875 compounds Chemical class 0.000 claims description 60
• 238000000034 method Methods 0.000 claims description 56
• 239000001257 hydrogen Substances 0.000 claims description 47
• 229910052739 hydrogen Inorganic materials 0.000 claims description 47
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 33
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 23
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
• 229910052799 carbon Inorganic materials 0.000 claims description 20
• 150000002431 hydrogen Chemical class 0.000 claims description 18
• 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 16
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 15
• 150000003839 salts Chemical class 0.000 claims description 14
• 125000000217 alkyl group Chemical group 0.000 claims description 11
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
• 206010028980 Neoplasm Diseases 0.000 claims description 10
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
• 125000003118 aryl group Chemical group 0.000 claims description 9
• 239000000543 intermediate Substances 0.000 claims description 8
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
• 239000011737 fluorine Substances 0.000 claims description 7
• 229910052731 fluorine Inorganic materials 0.000 claims description 7
• 229910052757 nitrogen Chemical group 0.000 claims description 7
• 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 6
• 125000001072 heteroaryl group Chemical group 0.000 claims description 6
• 125000000623 heterocyclic group Chemical group 0.000 claims description 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
• 150000001412 amines Chemical class 0.000 claims description 5
• 239000000460 chlorine Substances 0.000 claims description 5
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
• IBPQWZCJXXORJW-UHFFFAOYSA-N 3-methoxy-4-[[5-methyl-9-(2-methylcyclopentyl)-6-oxo-7,8-dihydropyrimido[4,5-b][1,4]diazepin-2-yl]amino]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound COC1=CC(C(=O)NC2CCN(C)CC2)=CC=C1NC(N=C12)=NC=C1N(C)C(=O)CCN2C1CCCC1C IBPQWZCJXXORJW-UHFFFAOYSA-N 0.000 claims description 4
• 210000000481 breast Anatomy 0.000 claims description 4
• 201000011510 cancer Diseases 0.000 claims description 4
• 229910052801 chlorine Inorganic materials 0.000 claims description 4
• 210000001072 colon Anatomy 0.000 claims description 4
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
• 125000005842 heteroatom Chemical group 0.000 claims description 4
• 229910052740 iodine Inorganic materials 0.000 claims description 4
• 210000004072 lung Anatomy 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
• JFRNFMQDZRWAQB-UHFFFAOYSA-N 4-[(9-cyclopentyl-5-methyl-6-oxo-7,8-dihydropyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxy-n-(1-methylpiperidin-4-yl)benzamide Chemical compound COC1=CC(C(=O)NC2CCN(C)CC2)=CC=C1NC(N=C12)=NC=C1N(C)C(=O)CCN2C1CCCC1 JFRNFMQDZRWAQB-UHFFFAOYSA-N 0.000 claims description 3
• 208000026310 Breast neoplasm Diseases 0.000 claims description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
• 229910052794 bromium Inorganic materials 0.000 claims description 3
• 208000029742 colonic neoplasm Diseases 0.000 claims description 3
• 239000003814 drug Substances 0.000 claims description 3
• 229910052736 halogen Inorganic materials 0.000 claims description 3
• 150000002367 halogens Chemical class 0.000 claims description 3
• 208000037841 lung tumor Diseases 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 230000008569 process Effects 0.000 claims description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 208000023958 prostate neoplasm Diseases 0.000 claims description 3
• 125000001424 substituent group Chemical group 0.000 claims description 3
• FQTWOSYKQWEEME-UHFFFAOYSA-N 3-methoxy-4-[(5-methyl-6-oxo-9-propan-2-yl-7,8-dihydropyrimido[4,5-b][1,4]diazepin-2-yl)amino]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C=1C=C(NC=2N=C3N(C(C)C)CCC(=O)N(C)C3=CN=2)C(OC)=CC=1C(=O)NC1CCN(C)CC1 FQTWOSYKQWEEME-UHFFFAOYSA-N 0.000 claims description 2
• AIPYUAKSIHTKGZ-UHFFFAOYSA-N 4-[(9-butyl-5-methyl-6-oxo-7,8-dihydropyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxy-n-(1-methylpiperidin-4-yl)benzamide Chemical compound N1=C2N(CCCC)CCC(=O)N(C)C2=CN=C1NC(C(=C1)OC)=CC=C1C(=O)NC1CCN(C)CC1 AIPYUAKSIHTKGZ-UHFFFAOYSA-N 0.000 claims description 2
• PQAUSXLMLXRHEX-UHFFFAOYSA-N 4-[(9-cyclobutyl-5-methyl-6-oxo-7,8-dihydropyrimido[4,5-b][1,4]diazepin-2-yl)amino]-n-(3-imidazol-1-ylpropyl)-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NCCCN2C=NC=C2)=CC=C1NC(N=C12)=NC=C1N(C)C(=O)CCN2C1CCC1 PQAUSXLMLXRHEX-UHFFFAOYSA-N 0.000 claims description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
• 239000011630 iodine Substances 0.000 claims description 2
• 229910052760 oxygen Inorganic materials 0.000 claims description 2
• 125000003386 piperidinyl group Chemical group 0.000 claims description 2
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
• 229920002554 vinyl polymer Polymers 0.000 claims description 2
• 125000002883 imidazolyl group Chemical group 0.000 claims 1
• 125000003698 tetramethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 529
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 307
• 230000002829 reductive effect Effects 0.000 description 216
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 199
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 147
• 239000000243 solution Substances 0.000 description 146
• JXYPNRIYAMXJSE-UHFFFAOYSA-N 1,4-diazepin-6-one Chemical compound O=C1C=NC=CN=C1 JXYPNRIYAMXJSE-UHFFFAOYSA-N 0.000 description 139
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 136
• 239000007787 solid Substances 0.000 description 116
• 238000010898 silica gel chromatography Methods 0.000 description 113
• 239000002253 acid Substances 0.000 description 112
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 107
• 239000010410 layer Substances 0.000 description 103
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 96
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 94
• 239000012267 brine Substances 0.000 description 82
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 82
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 79
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 75
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 75
• 238000000746 purification Methods 0.000 description 64
• 238000001914 filtration Methods 0.000 description 51
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
• 239000012044 organic layer Substances 0.000 description 44
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 40
• 239000002244 precipitate Substances 0.000 description 40
• GJJNFZOPTJVXID-UHFFFAOYSA-N 5,7,8,9-tetrahydropyrimido[4,5-b][1,4]diazepin-6-one Chemical compound N1C(=O)CCNC2=NC=NC=C21 GJJNFZOPTJVXID-UHFFFAOYSA-N 0.000 description 39
• 239000003921 oil Substances 0.000 description 38
• 235000019198 oils Nutrition 0.000 description 38
• ALOCUZOKRULSAA-UHFFFAOYSA-N 1-methylpiperidin-4-amine Chemical compound CN1CCC(N)CC1 ALOCUZOKRULSAA-UHFFFAOYSA-N 0.000 description 36
• PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 36
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 35
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
• 239000012071 phase Substances 0.000 description 35
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 33
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 33
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 32
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 32
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 32
• 125000004494 ethyl ester group Chemical group 0.000 description 32
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 31
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 28
• INUSQTPGSHFGHM-UHFFFAOYSA-N 2,4-dichloro-5-nitropyrimidine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1Cl INUSQTPGSHFGHM-UHFFFAOYSA-N 0.000 description 26
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 26
• 238000001816 cooling Methods 0.000 description 26
• 229910000028 potassium bicarbonate Inorganic materials 0.000 description 26
• 235000015497 potassium bicarbonate Nutrition 0.000 description 26
• 239000011736 potassium bicarbonate Substances 0.000 description 26
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 26
• 238000010992 reflux Methods 0.000 description 26
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 25
• 239000000284 extract Substances 0.000 description 25
• 239000000706 filtrate Substances 0.000 description 22
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 22
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 22
• 235000017557 sodium bicarbonate Nutrition 0.000 description 22
• JNFGLYJROFAOQP-UHFFFAOYSA-N 4-amino-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1N JNFGLYJROFAOQP-UHFFFAOYSA-N 0.000 description 21
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 21
• 150000004702 methyl esters Chemical class 0.000 description 21
• 239000000843 powder Substances 0.000 description 20
• 239000012312 sodium hydride Substances 0.000 description 20
• 229910000104 sodium hydride Inorganic materials 0.000 description 20
• 239000008346 aqueous phase Substances 0.000 description 19
• 239000012074 organic phase Substances 0.000 description 19
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 17
• 239000012298 atmosphere Substances 0.000 description 16
• 239000003054 catalyst Substances 0.000 description 16
• 238000005406 washing Methods 0.000 description 15
• 239000005711 Benzoic acid Substances 0.000 description 14
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
• 239000011541 reaction mixture Substances 0.000 description 14
• 239000000725 suspension Substances 0.000 description 14
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 13
• 150000002148 esters Chemical class 0.000 description 13
• 239000000463 material Substances 0.000 description 13
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 13
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 11
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 11
• 229910000024 caesium carbonate Inorganic materials 0.000 description 11
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 10
• 229940024606 amino acid Drugs 0.000 description 10
• 235000011114 ammonium hydroxide Nutrition 0.000 description 10
• 238000003756 stirring Methods 0.000 description 10
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 9
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
• 239000000908 ammonium hydroxide Substances 0.000 description 9
• WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 9
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
• 239000001632 sodium acetate Substances 0.000 description 9
• 235000017281 sodium acetate Nutrition 0.000 description 9
• 239000002904 solvent Substances 0.000 description 9
• POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical compound N1C=CC=NC=C1 POXWDTQUDZUOGP-UHFFFAOYSA-N 0.000 description 8
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 8
• XBYFLVPPIOYEJF-UHFFFAOYSA-N 4-amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1=C(N)C(OC)=CC(C(=O)NC2CCN(C)CC2)=C1 XBYFLVPPIOYEJF-UHFFFAOYSA-N 0.000 description 8
• FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 8
• XAYBXTPIBOXWLR-UHFFFAOYSA-N O.O.[Cl] Chemical compound O.O.[Cl] XAYBXTPIBOXWLR-UHFFFAOYSA-N 0.000 description 8
• 210000004027 cell Anatomy 0.000 description 8
• BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 8
• SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical class ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 8
• 239000006185 dispersion Substances 0.000 description 8
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 8
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 8
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
• 239000002671 adjuvant Substances 0.000 description 7
• 235000010233 benzoic acid Nutrition 0.000 description 7
• 238000006243 chemical reaction Methods 0.000 description 7
• 238000004587 chromatography analysis Methods 0.000 description 7
• 239000012230 colorless oil Substances 0.000 description 7
• ILUJQPXNXACGAN-UHFFFAOYSA-N ortho-methoxybenzoic acid Natural products COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 7
• 238000002360 preparation method Methods 0.000 description 7
• 239000011734 sodium Substances 0.000 description 7
• 229910052708 sodium Inorganic materials 0.000 description 7
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
• 238000001665 trituration Methods 0.000 description 7
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 6
• OFCBNMYNAHUDGE-UHFFFAOYSA-N 2-chloro-5-nitropyrimidine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1 OFCBNMYNAHUDGE-UHFFFAOYSA-N 0.000 description 6
• ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 6
• 125000003545 alkoxy group Chemical group 0.000 description 6
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