CA2687474A1 - Triazolyl aminopyrimidine compounds - Google Patents
Triazolyl aminopyrimidine compounds Download PDFInfo
- Publication number
- CA2687474A1 CA2687474A1 CA2687474A CA2687474A CA2687474A1 CA 2687474 A1 CA2687474 A1 CA 2687474A1 CA 2687474 A CA2687474 A CA 2687474A CA 2687474 A CA2687474 A CA 2687474A CA 2687474 A1 CA2687474 A1 CA 2687474A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- fluoro
- ethyl
- mmol
- alkyl
- Prior art date
- 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.)
- Abandoned
Links
- -1 Triazolyl aminopyrimidine compounds Chemical class 0.000 title claims abstract description 144
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 20
- 201000011510 cancer Diseases 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims description 175
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- 239000001257 hydrogen Substances 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 44
- 238000000034 method Methods 0.000 claims description 40
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 125000001153 fluoro group Chemical group F* 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 27
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 210000004072 lung Anatomy 0.000 claims description 6
- 201000001441 melanoma Diseases 0.000 claims description 6
- 210000000481 breast Anatomy 0.000 claims description 5
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims description 5
- 230000002357 endometrial effect Effects 0.000 claims description 5
- 230000002496 gastric effect Effects 0.000 claims description 5
- 208000005017 glioblastoma Diseases 0.000 claims description 5
- 208000006359 hepatoblastoma Diseases 0.000 claims description 5
- 230000002611 ovarian Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 210000002307 prostate Anatomy 0.000 claims description 5
- LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- 208000033781 Thyroid carcinoma Diseases 0.000 claims description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 201000010106 skin squamous cell carcinoma Diseases 0.000 claims description 4
- 201000002510 thyroid cancer Diseases 0.000 claims description 4
- 208000013077 thyroid gland carcinoma Diseases 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000006525 methoxy ethyl amino group Chemical group [H]N(*)C([H])([H])C([H])([H])OC([H])([H])[H] 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 198
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 171
- 239000000243 solution Substances 0.000 description 135
- 239000000203 mixture Substances 0.000 description 134
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 118
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 88
- 125000005605 benzo group Chemical group 0.000 description 88
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 84
- 238000003756 stirring Methods 0.000 description 77
- 239000007787 solid Substances 0.000 description 72
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 70
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 68
- 238000002360 preparation method Methods 0.000 description 65
- 229940093499 ethyl acetate Drugs 0.000 description 57
- 235000019439 ethyl acetate Nutrition 0.000 description 57
- 239000012141 concentrate Substances 0.000 description 56
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 50
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 46
- 229910052938 sodium sulfate Inorganic materials 0.000 description 46
- 235000011152 sodium sulphate Nutrition 0.000 description 46
- 238000004440 column chromatography Methods 0.000 description 42
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 42
- 239000000284 extract Substances 0.000 description 41
- 229920006395 saturated elastomer Polymers 0.000 description 36
- 239000011780 sodium chloride Substances 0.000 description 36
- 210000004027 cell Anatomy 0.000 description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 32
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 32
- 239000003921 oil Substances 0.000 description 29
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 239000000543 intermediate Substances 0.000 description 26
- 229910052757 nitrogen Inorganic materials 0.000 description 26
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 24
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 24
- 239000012044 organic layer Substances 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 22
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- 239000002904 solvent Substances 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000003818 flash chromatography Methods 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 15
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 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 13
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 12
- 229910000029 sodium carbonate Inorganic materials 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 11
- 229910052740 iodine Inorganic materials 0.000 description 11
- 239000010410 layer Substances 0.000 description 11
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 11
- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- 239000012043 crude product Substances 0.000 description 10
- 150000002431 hydrogen Chemical group 0.000 description 10
- UZWDCWONPYILKI-UHFFFAOYSA-N n-[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]-5-fluoro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-amine Chemical compound C1CN(CC)CCN1CC(C=N1)=CC=C1NC1=NC=C(F)C(C=2C=C3N(C(C)C)C(C)=NC3=C(F)C=2)=N1 UZWDCWONPYILKI-UHFFFAOYSA-N 0.000 description 10
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000000908 ammonium hydroxide Substances 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- 238000010791 quenching Methods 0.000 description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000011630 iodine Substances 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 230000000394 mitotic effect Effects 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000012312 sodium hydride Substances 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 7
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 229910021529 ammonia Inorganic materials 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- 239000007832 Na2SO4 Substances 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 6
- 238000012799 strong cation exchange Methods 0.000 description 6
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
- ZOSIXKLMVJHENK-UHFFFAOYSA-N 5-(bromomethyl)-2-fluoro-4-iodopyridine Chemical compound FC1=CC(I)=C(CBr)C=N1 ZOSIXKLMVJHENK-UHFFFAOYSA-N 0.000 description 5
- ZROZDUFRBQCNLE-UHFFFAOYSA-N 5-fluoro-4-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzothiophen-2-yl]-n-[2-(triazol-1-yl)ethyl]pyrimidin-2-amine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3N=NC=C3)N=1)F)=C2 ZROZDUFRBQCNLE-UHFFFAOYSA-N 0.000 description 5
- DVJNMERQFYKTEG-UHFFFAOYSA-N 6-fluoro-4-iodopyridin-3-ol Chemical compound OC1=CN=C(F)C=C1I DVJNMERQFYKTEG-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 229940086542 triethylamine Drugs 0.000 description 5
- BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 4
- CHEYEJGXQSHSFE-UHFFFAOYSA-N 2-(triazol-1-yl)ethanamine Chemical compound NCCN1C=CN=N1 CHEYEJGXQSHSFE-UHFFFAOYSA-N 0.000 description 4
- GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 description 4
- NOICDPBEDNMHQK-UHFFFAOYSA-N 7-bromo-1-benzothiophene Chemical compound BrC1=CC=CC2=C1SC=C2 NOICDPBEDNMHQK-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 101150041968 CDC13 gene Proteins 0.000 description 4
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 239000005909 Kieselgur Substances 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 4
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 4
- DAZXVJBJRMWXJP-UHFFFAOYSA-N n,n-dimethylethylamine Chemical compound CCN(C)C DAZXVJBJRMWXJP-UHFFFAOYSA-N 0.000 description 4
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- JZCYPDCIUJOAPG-UHFFFAOYSA-N tert-butyl n-[2-(6-fluoro-4-iodopyridin-3-yl)oxyethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOC1=CN=C(F)C=C1I JZCYPDCIUJOAPG-UHFFFAOYSA-N 0.000 description 4
- 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 4
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 4
- BAXMCVFPJFOSCM-UHFFFAOYSA-N 1-(6-fluoropyridin-3-yl)ethanol Chemical compound CC(O)C1=CC=C(F)N=C1 BAXMCVFPJFOSCM-UHFFFAOYSA-N 0.000 description 3
- NWDIURJMSKKSFV-UHFFFAOYSA-N 1-[4-(1-benzothiophen-7-yl)pyridin-3-yl]ethanamine Chemical compound CC(N)C1=CN=CC=C1C1=CC=CC2=C1SC=C2 NWDIURJMSKKSFV-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- TWCBACMXWWICMY-UHFFFAOYSA-N 2-(6-fluoro-4-iodopyridin-3-yl)acetonitrile Chemical compound FC1=CC(I)=C(CC#N)C=N1 TWCBACMXWWICMY-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- QBCHAVSIELFPPP-UHFFFAOYSA-N 2-chloro-4-iodo-5-(methoxymethoxy)pyridine Chemical compound COCOC1=CN=C(Cl)C=C1I QBCHAVSIELFPPP-UHFFFAOYSA-N 0.000 description 3
- UEHRAKHRJFMBOY-UHFFFAOYSA-N 3-(methoxymethoxy)pyridine Chemical compound COCOC1=CC=CN=C1 UEHRAKHRJFMBOY-UHFFFAOYSA-N 0.000 description 3
- AKAQWOZXUJXOIW-UHFFFAOYSA-N 4-[7-[2-chloro-5-[1-(methylamino)ethyl]pyridin-4-yl]-1-benzothiophen-2-yl]-n-[2-(triazol-1-yl)ethyl]pyrimidin-2-amine Chemical compound CNC(C)C1=CN=C(Cl)C=C1C1=CC=CC2=C1SC(C=1N=C(NCCN3N=NC=C3)N=CC=1)=C2 AKAQWOZXUJXOIW-UHFFFAOYSA-N 0.000 description 3
- DPVWKVPWHZMNQD-UHFFFAOYSA-N 5-(1-azidoethyl)-2-fluoropyridine Chemical compound [N-]=[N+]=NC(C)C1=CC=C(F)N=C1 DPVWKVPWHZMNQD-UHFFFAOYSA-N 0.000 description 3
- SWDDSHHONTUPFG-UHFFFAOYSA-N 5-cyclopropyl-2-fluoro-3-iodopyridine Chemical compound C1=C(I)C(F)=NC=C1C1CC1 SWDDSHHONTUPFG-UHFFFAOYSA-N 0.000 description 3
- XWYBMCCCOJQFBM-UHFFFAOYSA-N 6-fluoro-4-iodopyridin-3-amine Chemical compound NC1=CN=C(F)C=C1I XWYBMCCCOJQFBM-UHFFFAOYSA-N 0.000 description 3
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- HXYYHEHVBPUJEC-QMMMGPOBSA-N tert-butyl n-[(1s)-1-(6-fluoro-4-iodopyridin-3-yl)ethyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)[C@@H](C)C1=CN=C(F)C=C1I HXYYHEHVBPUJEC-QMMMGPOBSA-N 0.000 description 1
- PGXJXKZUELCAQH-UHFFFAOYSA-N tert-butyl n-[1-(4-iodo-6-methylpyridin-3-yl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C)C1=CN=C(C)C=C1I PGXJXKZUELCAQH-UHFFFAOYSA-N 0.000 description 1
- KQSWZIGWXPHDFK-UHFFFAOYSA-N tert-butyl n-[1-(6-chloropyridin-3-yl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C)C1=CC=C(Cl)N=C1 KQSWZIGWXPHDFK-UHFFFAOYSA-N 0.000 description 1
- HXYYHEHVBPUJEC-UHFFFAOYSA-N tert-butyl n-[1-(6-fluoro-4-iodopyridin-3-yl)ethyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)C(C)C1=CN=C(F)C=C1I HXYYHEHVBPUJEC-UHFFFAOYSA-N 0.000 description 1
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- PDKAOKKOVJTBKB-UHFFFAOYSA-N tert-butyl n-[1-[[6-fluoro-4-[2-[5-fluoro-2-[2-(triazol-1-yl)ethylamino]pyrimidin-4-yl]-1-benzothiophen-7-yl]pyridin-3-yl]methyl]pyrrolidin-3-yl]-n-methylcarbamate Chemical compound C1C(N(C)C(=O)OC(C)(C)C)CCN1CC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3N=NC=C3)N=1)F)=C2 PDKAOKKOVJTBKB-UHFFFAOYSA-N 0.000 description 1
- BUYJXCTYRVNFER-UHFFFAOYSA-N tert-butyl n-[[6-fluoro-4-[2-[5-fluoro-2-[2-(triazol-1-yl)ethylamino]pyrimidin-4-yl]-1-benzothiophen-7-yl]pyridin-3-yl]methyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)CC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3N=NC=C3)N=1)F)=C2 BUYJXCTYRVNFER-UHFFFAOYSA-N 0.000 description 1
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- GMRIOAVKKGNMMV-UHFFFAOYSA-N tetrabutylazanium;azide Chemical compound [N-]=[N+]=[N-].CCCC[N+](CCCC)(CCCC)CCCC GMRIOAVKKGNMMV-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US93833307P | 2007-05-16 | 2007-05-16 | |
| US60/938,333 | 2007-05-16 | ||
| PCT/US2008/062799 WO2008144222A2 (en) | 2007-05-16 | 2008-05-07 | Triazolyl aminopyrimidine compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2687474A1 true CA2687474A1 (en) | 2008-11-27 |
Family
ID=39967594
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2687474A Abandoned CA2687474A1 (en) | 2007-05-16 | 2008-05-07 | Triazolyl aminopyrimidine compounds |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US8114872B2 (enExample) |
| EP (1) | EP2155735A2 (enExample) |
| JP (1) | JP5204838B2 (enExample) |
| KR (1) | KR101131254B1 (enExample) |
| CN (1) | CN101679396B (enExample) |
| AR (1) | AR066472A1 (enExample) |
| AU (1) | AU2008254318B2 (enExample) |
| BR (1) | BRPI0811611A2 (enExample) |
| CA (1) | CA2687474A1 (enExample) |
| CL (1) | CL2008001322A1 (enExample) |
| EA (1) | EA015574B1 (enExample) |
| MX (1) | MX2009012233A (enExample) |
| PE (1) | PE20090803A1 (enExample) |
| TW (1) | TW200902012A (enExample) |
| WO (1) | WO2008144222A2 (enExample) |
Families Citing this family (5)
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|---|---|---|---|---|
| JP2010513553A (ja) | 2006-12-21 | 2010-04-30 | イーライ リリー アンド カンパニー | 癌治療用イミダゾリジノニルアミノピリミジン化合物 |
| CN101563342B (zh) | 2006-12-21 | 2012-09-05 | 伊莱利利公司 | 用于治疗癌症的咪唑啉酮基氨基嘧啶化合物 |
| MX2009012228A (es) * | 2007-05-16 | 2009-12-01 | Lilly Co Eli | Compuesto de triazolil aminopirimidina. |
| EA015574B1 (ru) | 2007-05-16 | 2011-10-31 | Эли Лилли Энд Компани | Триазолиламинопиримидиновые соединения |
| MX374634B (es) | 2013-04-15 | 2025-03-06 | Fmc Corp Star | Amidas fungicidas. |
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|---|---|---|---|---|
| US4929726A (en) | 1988-02-09 | 1990-05-29 | Georgia State University Foundation, Inc. | Novel diazines and their method of preparation |
| WO2004063192A1 (en) | 2003-01-10 | 2004-07-29 | Pharmacopeia Drug Discovery, Inc. | Imidazolyl pyrimidine derivatives useful as il-8 receptor modulators |
| GB0308466D0 (en) | 2003-04-11 | 2003-05-21 | Novartis Ag | Organic compounds |
| US7521457B2 (en) * | 2004-08-20 | 2009-04-21 | Boehringer Ingelheim International Gmbh | Pyrimidines as PLK inhibitors |
| JP2008510771A (ja) * | 2004-08-27 | 2008-04-10 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ジヒドロプテリジノン、その製造方法および医薬薬剤としてのその使用 |
| MX2007007032A (es) * | 2004-12-17 | 2007-07-04 | Amgen Inc | Compuestos de aminopirimidina y metodos de uso. |
| TW200800201A (en) | 2005-11-18 | 2008-01-01 | Lilly Co Eli | Pyrimidinyl benzothiophene compounds |
| US8008481B2 (en) | 2006-03-31 | 2011-08-30 | Ericsson Anna M | Indazole compounds |
| CN101563342B (zh) | 2006-12-21 | 2012-09-05 | 伊莱利利公司 | 用于治疗癌症的咪唑啉酮基氨基嘧啶化合物 |
| MX2009012228A (es) | 2007-05-16 | 2009-12-01 | Lilly Co Eli | Compuesto de triazolil aminopirimidina. |
| EA015574B1 (ru) | 2007-05-16 | 2011-10-31 | Эли Лилли Энд Компани | Триазолиламинопиримидиновые соединения |
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2008
- 2008-05-07 EA EA200971067A patent/EA015574B1/ru not_active IP Right Cessation
- 2008-05-07 CL CL2008001322A patent/CL2008001322A1/es unknown
- 2008-05-07 AR ARP080101931A patent/AR066472A1/es unknown
- 2008-05-07 US US12/596,957 patent/US8114872B2/en not_active Expired - Fee Related
- 2008-05-07 CN CN2008800159078A patent/CN101679396B/zh not_active Expired - Fee Related
- 2008-05-07 TW TW097116887A patent/TW200902012A/zh unknown
- 2008-05-07 JP JP2010508499A patent/JP5204838B2/ja not_active Expired - Fee Related
- 2008-05-07 EP EP08755094A patent/EP2155735A2/en not_active Withdrawn
- 2008-05-07 MX MX2009012233A patent/MX2009012233A/es active IP Right Grant
- 2008-05-07 AU AU2008254318A patent/AU2008254318B2/en not_active Ceased
- 2008-05-07 BR BRPI0811611-3A2A patent/BRPI0811611A2/pt not_active IP Right Cessation
- 2008-05-07 PE PE2008000797A patent/PE20090803A1/es not_active Application Discontinuation
- 2008-05-07 WO PCT/US2008/062799 patent/WO2008144222A2/en not_active Ceased
- 2008-05-07 KR KR1020097023738A patent/KR101131254B1/ko not_active Expired - Fee Related
- 2008-05-07 CA CA2687474A patent/CA2687474A1/en not_active Abandoned
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| WO2008144222A3 (en) | 2009-01-15 |
| US20100130466A1 (en) | 2010-05-27 |
| MX2009012233A (es) | 2009-12-01 |
| EA200971067A1 (ru) | 2010-04-30 |
| CN101679396B (zh) | 2012-06-06 |
| AU2008254318B2 (en) | 2012-04-05 |
| AU2008254318A1 (en) | 2008-11-27 |
| JP2010527364A (ja) | 2010-08-12 |
| JP5204838B2 (ja) | 2013-06-05 |
| US8114872B2 (en) | 2012-02-14 |
| PE20090803A1 (es) | 2009-07-11 |
| CN101679396A (zh) | 2010-03-24 |
| EA015574B1 (ru) | 2011-10-31 |
| TW200902012A (en) | 2009-01-16 |
| CL2008001322A1 (es) | 2009-05-22 |
| AR066472A1 (es) | 2009-08-19 |
| BRPI0811611A2 (pt) | 2014-11-04 |
| WO2008144222A2 (en) | 2008-11-27 |
| KR101131254B1 (ko) | 2012-04-24 |
| EP2155735A2 (en) | 2010-02-24 |
| KR20090130246A (ko) | 2009-12-21 |
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