RU2643811C2 - Способ получения гидроксилированных циклопентилпиримидиновых соединений - Google Patents
Способ получения гидроксилированных циклопентилпиримидиновых соединений Download PDFInfo
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- RU2643811C2 RU2643811C2 RU2014151050A RU2014151050A RU2643811C2 RU 2643811 C2 RU2643811 C2 RU 2643811C2 RU 2014151050 A RU2014151050 A RU 2014151050A RU 2014151050 A RU2014151050 A RU 2014151050A RU 2643811 C2 RU2643811 C2 RU 2643811C2
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- compound
- formula
- salt
- alkyl
- substituted
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- 238000004519 manufacturing process Methods 0.000 title description 7
- KHXLVDUXFUNEQQ-UHFFFAOYSA-N 2-cyclopentylpyrimidine Chemical class C1CCCC1C1=NC=CC=N1 KHXLVDUXFUNEQQ-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 107
- 150000003839 salts Chemical class 0.000 claims abstract description 74
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 54
- 238000000034 method Methods 0.000 claims abstract description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 32
- 239000001257 hydrogen Substances 0.000 claims abstract description 32
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 23
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 16
- 125000004429 atom Chemical group 0.000 claims abstract description 15
- 229910052744 lithium Inorganic materials 0.000 claims abstract description 13
- 239000011777 magnesium Substances 0.000 claims abstract description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 12
- 229910052749 magnesium Inorganic materials 0.000 claims abstract description 12
- 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 abstract description 8
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 6
- 150000004791 alkyl magnesium halides Chemical class 0.000 claims abstract 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims description 56
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 15
- 229910052740 iodine Inorganic materials 0.000 claims description 15
- 239000011630 iodine Substances 0.000 claims description 15
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- 150000002431 hydrogen Chemical group 0.000 claims description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 6
- 230000002083 iodinating effect Effects 0.000 claims description 5
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- OJQZSTYCPGIRDK-LLVKDONJSA-N (3R)-3-[4-iodo-6-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]pyrimidin-5-yl]butanoic acid Chemical compound C[C@H](CC(O)=O)c1c(I)ncnc1N1CCN(CC1)C(=O)OC(C)(C)C OJQZSTYCPGIRDK-LLVKDONJSA-N 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- OIUUNRAGHYZJTI-CYBMUJFWSA-N tert-butyl 4-[6-iodo-5-[(2r)-4-[methoxy(methyl)amino]-4-oxobutan-2-yl]pyrimidin-4-yl]piperazine-1-carboxylate Chemical compound CON(C)C(=O)C[C@@H](C)C1=C(I)N=CN=C1N1CCN(C(=O)OC(C)(C)C)CC1 OIUUNRAGHYZJTI-CYBMUJFWSA-N 0.000 claims description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims 2
- UUIQMZJEGPQKFD-UHFFFAOYSA-N Methyl butyrate Chemical compound CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 claims 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 claims 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 claims 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 1
- -1 t-butoxycarbonyl Chemical group 0.000 abstract description 81
- 238000002360 preparation method Methods 0.000 abstract description 6
- 239000000543 intermediate Substances 0.000 abstract description 5
- 206010028980 Neoplasm Diseases 0.000 abstract description 3
- 125000001246 bromo group Chemical group Br* 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 201000011510 cancer Diseases 0.000 abstract description 2
- 201000010099 disease Diseases 0.000 abstract description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 229940043355 kinase inhibitor Drugs 0.000 abstract description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 abstract description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 125000000753 cycloalkyl group Chemical group 0.000 description 26
- 125000003342 alkenyl group Chemical group 0.000 description 21
- 125000000304 alkynyl group Chemical group 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- 125000003118 aryl group Chemical group 0.000 description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 15
- 125000006239 protecting group Chemical group 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 13
- 125000001424 substituent group Chemical group 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 125000001072 heteroaryl group Chemical group 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 229910052736 halogen Inorganic materials 0.000 description 8
- 150000002367 halogens Chemical group 0.000 description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 108091008611 Protein Kinase B Proteins 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 125000003545 alkoxy group Chemical group 0.000 description 7
- 125000006413 ring segment Chemical group 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 5
- 239000004215 Carbon black (E152) Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 125000004043 oxo group Chemical group O=* 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 235000009518 sodium iodide Nutrition 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- GRZXWCHAXNAUHY-NSISKUIASA-N (2S)-2-(4-chlorophenyl)-1-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]-1-piperazinyl]-3-(propan-2-ylamino)-1-propanone Chemical compound C1([C@H](C(=O)N2CCN(CC2)C=2C=3[C@H](C)C[C@@H](O)C=3N=CN=2)CNC(C)C)=CC=C(Cl)C=C1 GRZXWCHAXNAUHY-NSISKUIASA-N 0.000 description 3
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 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 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 3
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000003107 substituted aryl group Chemical group 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- FYSLHZSJYXKKMC-LLVKDONJSA-N tert-butyl 4-[(5r)-5-methyl-7-oxo-5,6-dihydrocyclopenta[d]pyrimidin-4-yl]piperazine-1-carboxylate Chemical compound C([C@H](C=12)C)C(=O)C2=NC=NC=1N1CCN(C(=O)OC(C)(C)C)CC1 FYSLHZSJYXKKMC-LLVKDONJSA-N 0.000 description 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- 125000004398 2-methyl-2-butyl group Chemical group CC(C)(CC)* 0.000 description 2
- 125000004918 2-methyl-2-pentyl group Chemical group CC(C)(CCC)* 0.000 description 2
- 125000004922 2-methyl-3-pentyl group Chemical group CC(C)C(CC)* 0.000 description 2
- 125000004917 3-methyl-2-butyl group Chemical group CC(C(C)*)C 0.000 description 2
- 125000004919 3-methyl-2-pentyl group Chemical group CC(C(C)*)CC 0.000 description 2
- 125000004921 3-methyl-3-pentyl group Chemical group CC(CC)(CC)* 0.000 description 2
- 125000004920 4-methyl-2-pentyl group Chemical group CC(CC(C)*)C 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 238000010533 azeotropic distillation Methods 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
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- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
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- NWDXDEBDJICFAS-UHFFFAOYSA-N dicyclopentylmethanone Chemical compound C1CCCC1C(=O)C1CCCC1 NWDXDEBDJICFAS-UHFFFAOYSA-N 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
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- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
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- 239000012467 final product Substances 0.000 description 1
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- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
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- 125000003838 furazanyl group Chemical group 0.000 description 1
- 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
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- 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
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- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
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- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
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- 238000011065 in-situ storage Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
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- 239000003112 inhibitor Substances 0.000 description 1
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- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical class OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
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- 239000004310 lactic acid Substances 0.000 description 1
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- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- RYEXTBOQKFUPOE-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].CC[CH2-] RYEXTBOQKFUPOE-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
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- XLADYKVTZFVWDT-UHFFFAOYSA-N methyl 3-(4-hydroxy-6-oxo-1h-pyrimidin-5-yl)butanoate Chemical compound COC(=O)CC(C)C1=C(O)N=CN=C1O XLADYKVTZFVWDT-UHFFFAOYSA-N 0.000 description 1
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- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
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- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
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- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical class [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000011916 stereoselective reduction Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical group NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
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- 238000003786 synthesis reaction Methods 0.000 description 1
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- 239000011975 tartaric acid Substances 0.000 description 1
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- 150000003892 tartrate salts Chemical class 0.000 description 1
- XONQUPLAHVNKOI-GFCCVEGCSA-N tert-butyl 4-[6-iodo-5-[(2R)-4-methoxy-4-oxobutan-2-yl]pyrimidin-4-yl]piperazine-1-carboxylate Chemical compound COC(=O)C[C@@H](C)c1c(I)ncnc1N1CCN(CC1)C(=O)OC(C)(C)C XONQUPLAHVNKOI-GFCCVEGCSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
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- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
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- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000005308 thiazepinyl group Chemical group S1N=C(C=CC=C1)* 0.000 description 1
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- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/30—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (5)
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| US201261648473P | 2012-05-17 | 2012-05-17 | |
| US61/648,473 | 2012-05-17 | ||
| US201361785122P | 2013-03-14 | 2013-03-14 | |
| US61/785,122 | 2013-03-14 | ||
| PCT/US2013/041666 WO2013173768A1 (en) | 2012-05-17 | 2013-05-17 | Process for making hydroxylated cyclopentylpyrimidine compounds |
Publications (2)
| Publication Number | Publication Date |
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| RU2014151050A RU2014151050A (ru) | 2016-07-10 |
| RU2643811C2 true RU2643811C2 (ru) | 2018-02-06 |
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| SI (1) | SI2861582T1 (enExample) |
| WO (1) | WO2013173768A1 (enExample) |
| ZA (1) | ZA201409261B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2712224C2 (ru) * | 2014-09-26 | 2020-01-27 | Ф. Хоффманн-Ля Рош Аг | Способы получения (циклопентил[d]пиримидин-4-ил)пиперазиновых соединений |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2861582T3 (en) | 2012-05-17 | 2016-08-22 | Array Biopharma Inc | A process for preparing hydroxylated compounds cyclopentylpyrimidin |
| SG11201407618VA (en) | 2012-05-17 | 2015-01-29 | Genentech Inc | Amorphous form of an akt inhibiting pyrimidinyl - cyclopentane compound, compositions and methods thereof |
| EP2850200A1 (en) | 2012-05-17 | 2015-03-25 | Genentech, Inc. | Process of making hydroxylated cyclopentapyrimidine compounds and salts thereof |
| ES2588878T3 (es) | 2012-05-17 | 2016-11-07 | Array Biopharma, Inc. | Proceso para preparar compuestos de ciclopentilpirimidina hidroxilada |
| CN105899492B (zh) | 2013-11-15 | 2021-08-24 | 豪夫迈·罗氏有限公司 | 用于制备嘧啶基环戊烷化合物的方法 |
| KR102766096B1 (ko) | 2016-08-10 | 2025-02-12 | 에프. 호프만-라 로슈 아게 | Akt 단백질 키나아제 저해제를 포함하는 약학 조성물 |
| CN115916758A (zh) | 2020-06-16 | 2023-04-04 | 豪夫迈·罗氏有限公司 | 用于制备羟基化环戊基嘧啶化合物的方法 |
| KR102689151B1 (ko) * | 2021-09-06 | 2024-07-29 | 연세대학교 산학협력단 | Akt 신호경로 억제제를 유효성분으로 포함하는 아토피피부염의 예방 또는 치료용 조성물 |
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| JP2001524079A (ja) | 1997-04-07 | 2001-11-27 | メルク エンド カンパニー インコーポレーテッド | ガンの治療方法 |
| US6201023B1 (en) | 1997-06-10 | 2001-03-13 | Agrogene Ltd. | Methods and compositions to protect crops against plant parasitic nematodes |
| EP0982300A3 (en) | 1998-07-29 | 2000-03-08 | Societe Civile Bioprojet | Non-imidazole alkylamines as histamine H3 - receptor ligands and their therapeutic applications |
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| EP2209775A1 (en) | 2007-10-09 | 2010-07-28 | UCB Pharma, S.A. | Heterobicyclic compounds as histamine h4-receptor antagonists |
| JP5734956B2 (ja) | 2009-04-15 | 2015-06-17 | アッヴィ・インコーポレイテッド | 抗ウィルス化合物 |
| US9050334B2 (en) | 2010-07-16 | 2015-06-09 | Innov88 Llc | MIF inhibitors and their uses |
| WO2012177925A1 (en) | 2011-06-21 | 2012-12-27 | The Board Institute, Inc. | Akt inhibitors for treating cancer expressing a magi3 - akt3 fusion gene |
| EP2850200A1 (en) | 2012-05-17 | 2015-03-25 | Genentech, Inc. | Process of making hydroxylated cyclopentapyrimidine compounds and salts thereof |
| SG11201407618VA (en) | 2012-05-17 | 2015-01-29 | Genentech Inc | Amorphous form of an akt inhibiting pyrimidinyl - cyclopentane compound, compositions and methods thereof |
| KR102074535B1 (ko) | 2012-05-17 | 2020-02-06 | 제넨테크, 인크. | 아미노산 화합물의 제조 방법 |
| DK2861582T3 (en) | 2012-05-17 | 2016-08-22 | Array Biopharma Inc | A process for preparing hydroxylated compounds cyclopentylpyrimidin |
| ES2588878T3 (es) | 2012-05-17 | 2016-11-07 | Array Biopharma, Inc. | Proceso para preparar compuestos de ciclopentilpirimidina hidroxilada |
| US20140121193A1 (en) | 2012-11-01 | 2014-05-01 | Robert S. Katz | Methods for treating fibromyalgia |
| CA2901577A1 (en) | 2013-02-18 | 2014-08-21 | The Scripps Research Institute | Modulators of vasopressin receptors with therapeutic potential |
| US10131637B2 (en) | 2013-03-15 | 2018-11-20 | Shifa Biomedical Corporation | Anti-PCSK9 compounds and methods for the treatment and/or prevention of cardiovascular diseases |
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2013
- 2013-05-17 DK DK13725042.9T patent/DK2861582T3/en active
- 2013-05-17 US US14/401,087 patent/US9416110B2/en active Active
- 2013-05-17 EP EP13725042.9A patent/EP2861582B1/en active Active
- 2013-05-17 WO PCT/US2013/041666 patent/WO2013173768A1/en not_active Ceased
- 2013-05-17 MY MYPI2014703415A patent/MY169028A/en unknown
- 2013-05-17 JP JP2015512900A patent/JP6284928B2/ja active Active
- 2013-05-17 SG SG11201407616TA patent/SG11201407616TA/en unknown
- 2013-05-17 AU AU2013262505A patent/AU2013262505B2/en active Active
- 2013-05-17 ES ES13725042.9T patent/ES2582557T3/es active Active
- 2013-05-17 CA CA2873654A patent/CA2873654C/en active Active
- 2013-05-17 SI SI201330261A patent/SI2861582T1/sl unknown
- 2013-05-17 CN CN201380038057.4A patent/CN104470913B/zh active Active
- 2013-05-17 PL PL13725042.9T patent/PL2861582T3/pl unknown
- 2013-05-17 KR KR1020147035427A patent/KR102067850B1/ko active Active
- 2013-05-17 MX MX2014013862A patent/MX353384B/es active IP Right Grant
- 2013-05-17 BR BR112014028589-6A patent/BR112014028589B1/pt active IP Right Grant
- 2013-05-17 NZ NZ702935A patent/NZ702935A/en not_active IP Right Cessation
- 2013-05-17 RU RU2014151050A patent/RU2643811C2/ru active
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2014
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- 2014-12-15 ZA ZA2014/09261A patent/ZA201409261B/en unknown
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2016
- 2016-07-07 US US15/204,715 patent/US9676730B2/en active Active
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2017
- 2017-05-11 US US15/593,064 patent/US9790190B2/en active Active
- 2017-10-12 US US15/782,620 patent/US20180258054A1/en not_active Abandoned
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| EP1188754A1 (en) * | 1999-06-03 | 2002-03-20 | Teikoku Hormone Mfg. Co., Ltd. | Substituted pyrazole compounds |
| WO2008006040A1 (en) * | 2006-07-06 | 2008-01-10 | Array Biopharma Inc. | Hydroxylated and methoxylated cyclopenta [d] pyrimidines as akt protein kinase inhibitors |
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| RU2712224C2 (ru) * | 2014-09-26 | 2020-01-27 | Ф. Хоффманн-Ля Рош Аг | Способы получения (циклопентил[d]пиримидин-4-ил)пиперазиновых соединений |
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