CN114007606A - 呋喃并咪唑并吡啶类化合物的合成方法、多晶型物、及盐的多晶型物 - Google Patents
呋喃并咪唑并吡啶类化合物的合成方法、多晶型物、及盐的多晶型物 Download PDFInfo
- Publication number
- CN114007606A CN114007606A CN202080037087.3A CN202080037087A CN114007606A CN 114007606 A CN114007606 A CN 114007606A CN 202080037087 A CN202080037087 A CN 202080037087A CN 114007606 A CN114007606 A CN 114007606A
- Authority
- CN
- China
- Prior art keywords
- formula
- compound
- degrees
- stirring
- solution
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims description 47
- 230000008569 process Effects 0.000 title claims description 18
- 150000003839 salts Chemical class 0.000 title abstract description 14
- 230000015572 biosynthetic process Effects 0.000 title description 6
- 238000003786 synthesis reaction Methods 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 852
- 239000013078 crystal Substances 0.000 claims abstract description 269
- 238000006243 chemical reaction Methods 0.000 claims abstract description 101
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims abstract description 9
- 230000009467 reduction Effects 0.000 claims abstract description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 416
- 239000000243 solution Substances 0.000 claims description 305
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 231
- 239000007787 solid Substances 0.000 claims description 217
- 238000003756 stirring Methods 0.000 claims description 217
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 180
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 169
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 168
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 147
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 106
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 99
- 239000012065 filter cake Substances 0.000 claims description 93
- 238000001816 cooling Methods 0.000 claims description 88
- 239000002904 solvent Substances 0.000 claims description 87
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 84
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 82
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 80
- 238000010438 heat treatment Methods 0.000 claims description 80
- 238000002360 preparation method Methods 0.000 claims description 80
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 58
- 229910019142 PO4 Inorganic materials 0.000 claims description 57
- 239000010452 phosphate Substances 0.000 claims description 57
- 238000001035 drying Methods 0.000 claims description 56
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 55
- 229910052757 nitrogen Inorganic materials 0.000 claims description 53
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 52
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 51
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 50
- 229940095064 tartrate Drugs 0.000 claims description 46
- 238000001914 filtration Methods 0.000 claims description 45
- 239000000725 suspension Substances 0.000 claims description 44
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 42
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 claims description 41
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 39
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 39
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 38
- 238000010992 reflux Methods 0.000 claims description 37
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 36
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 35
- 238000002386 leaching Methods 0.000 claims description 33
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 33
- -1 compound hydrochloride Chemical class 0.000 claims description 32
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 30
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 29
- 150000003840 hydrochlorides Chemical group 0.000 claims description 29
- 238000005119 centrifugation Methods 0.000 claims description 28
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 26
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 25
- 239000011975 tartaric acid Substances 0.000 claims description 24
- 235000002906 tartaric acid Nutrition 0.000 claims description 24
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 23
- 238000004519 manufacturing process Methods 0.000 claims description 22
- HDPNBNXLBDFELL-UHFFFAOYSA-N 1,1,1-trimethoxyethane Chemical compound COC(C)(OC)OC HDPNBNXLBDFELL-UHFFFAOYSA-N 0.000 claims description 21
- 239000000047 product Substances 0.000 claims description 21
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 21
- 239000012141 concentrate Substances 0.000 claims description 19
- 239000000706 filtrate Substances 0.000 claims description 18
- 239000012296 anti-solvent Substances 0.000 claims description 17
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 16
- 239000000463 material Substances 0.000 claims description 16
- 238000004321 preservation Methods 0.000 claims description 15
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 14
- 229940077388 benzenesulfonate Drugs 0.000 claims description 14
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 14
- 150000003892 tartrate salts Chemical class 0.000 claims description 14
- 238000005406 washing Methods 0.000 claims description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 13
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 13
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 12
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 11
- 239000012043 crude product Substances 0.000 claims description 10
- 238000001291 vacuum drying Methods 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 238000001953 recrystallisation Methods 0.000 claims description 9
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 8
- 239000001530 fumaric acid Substances 0.000 claims description 8
- 239000011259 mixed solution Substances 0.000 claims description 8
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 238000000746 purification Methods 0.000 claims description 7
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 229910052710 silicon Inorganic materials 0.000 claims description 4
- 239000010703 silicon Substances 0.000 claims description 4
- 230000009466 transformation Effects 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 3
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 3
- 229940011051 isopropyl acetate Drugs 0.000 claims description 3
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims description 2
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 claims description 2
- 230000002062 proliferating effect Effects 0.000 claims description 2
- 239000002516 radical scavenger Substances 0.000 claims description 2
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 claims 1
- 238000009776 industrial production Methods 0.000 abstract description 5
- 102000002295 Janus Kinase 1 Human genes 0.000 abstract description 3
- 108010000837 Janus Kinase 1 Proteins 0.000 abstract description 3
- 108010010057 TYK2 Kinase Proteins 0.000 abstract description 3
- 102000015774 TYK2 Kinase Human genes 0.000 abstract description 3
- 229940043355 kinase inhibitor Drugs 0.000 abstract description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 abstract description 3
- JVWXVJOIUKQBOJ-NWDGAFQWSA-N 2-[(2R,5S)-5-(4-methyl-12-oxa-3,5,8-triazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,10-pentaen-3-yl)oxan-2-yl]acetonitrile Chemical compound CC1=NC=2C(=C3C(=NC=2)C=CO3)N1[C@H]1CC[C@@H](OC1)CC#N JVWXVJOIUKQBOJ-NWDGAFQWSA-N 0.000 abstract description 2
- 238000009509 drug development Methods 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract description 2
- AQCQKDBQDZRGAH-UHFFFAOYSA-N 7-chloro-6-nitrofuro[3,2-b]pyridine Chemical compound C1(=C(Cl)C=2OC=CC=2N=C1)N(=O)=O AQCQKDBQDZRGAH-UHFFFAOYSA-N 0.000 abstract 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 abstract 1
- 238000006722 reduction reaction Methods 0.000 abstract 1
- 238000007363 ring formation reaction Methods 0.000 abstract 1
- 239000007858 starting material Substances 0.000 abstract 1
- 238000010189 synthetic method Methods 0.000 abstract 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 75
- 239000000523 sample Substances 0.000 description 68
- 238000000113 differential scanning calorimetry Methods 0.000 description 52
- 235000019441 ethanol Nutrition 0.000 description 49
- 238000012360 testing method Methods 0.000 description 30
- 238000003760 magnetic stirring Methods 0.000 description 27
- 238000004448 titration Methods 0.000 description 26
- 238000005481 NMR spectroscopy Methods 0.000 description 21
- 238000002390 rotary evaporation Methods 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 238000005070 sampling Methods 0.000 description 16
- 238000010521 absorption reaction Methods 0.000 description 15
- 238000004090 dissolution Methods 0.000 description 15
- 238000005303 weighing Methods 0.000 description 15
- 239000012295 chemical reaction liquid Substances 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000007788 liquid Substances 0.000 description 12
- 238000001228 spectrum Methods 0.000 description 12
- 238000001514 detection method Methods 0.000 description 11
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 238000006073 displacement reaction Methods 0.000 description 9
- 108091000080 Phosphotransferase Proteins 0.000 description 8
- 239000012535 impurity Substances 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 102000020233 phosphotransferase Human genes 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000012488 sample solution Substances 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 239000001358 L(+)-tartaric acid Substances 0.000 description 5
- 235000011002 L(+)-tartaric acid Nutrition 0.000 description 5
- FEWJPZIEWOKRBE-LWMBPPNESA-N L-(+)-Tartaric acid Natural products OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 5
- 230000001276 controlling effect Effects 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 238000001757 thermogravimetry curve Methods 0.000 description 5
- 101000844245 Homo sapiens Non-receptor tyrosine-protein kinase TYK2 Proteins 0.000 description 4
- 102100032028 Non-receptor tyrosine-protein kinase TYK2 Human genes 0.000 description 4
- 230000001133 acceleration Effects 0.000 description 4
- 150000001860 citric acid derivatives Chemical group 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 238000004255 ion exchange chromatography Methods 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- IWZKICVEHNUQTL-UHFFFAOYSA-M potassium hydrogen phthalate Chemical compound [K+].OC(=O)C1=CC=CC=C1C([O-])=O IWZKICVEHNUQTL-UHFFFAOYSA-M 0.000 description 4
- CHWRSCGUEQEHOH-UHFFFAOYSA-N potassium oxide Chemical compound [O-2].[K+].[K+] CHWRSCGUEQEHOH-UHFFFAOYSA-N 0.000 description 4
- 229910001950 potassium oxide Inorganic materials 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000003825 pressing Methods 0.000 description 4
- 229910001220 stainless steel Inorganic materials 0.000 description 4
- 239000010935 stainless steel Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 238000000967 suction filtration Methods 0.000 description 4
- 238000002411 thermogravimetry Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 101150069380 JAK3 gene Proteins 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 102000003675 cytokine receptors Human genes 0.000 description 3
- 108010057085 cytokine receptors Proteins 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 239000007791 liquid phase Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- ZQBVUULQVWCGDQ-UHFFFAOYSA-N propan-1-ol;propan-2-ol Chemical compound CCCO.CC(C)O ZQBVUULQVWCGDQ-UHFFFAOYSA-N 0.000 description 3
- 238000004537 pulping Methods 0.000 description 3
- 238000007670 refining Methods 0.000 description 3
- 238000010583 slow cooling Methods 0.000 description 3
- ILSYTMBVJDPAKS-ZVGUSBNCSA-N (2R,3R)-2,3-dihydroxybutanedioic acid propan-2-one Chemical compound CC(C)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O ILSYTMBVJDPAKS-ZVGUSBNCSA-N 0.000 description 2
- DLXLXJXLPPYFLA-ZVGUSBNCSA-N C([C@H](O)[C@@H](O)C(=O)O)(=O)O.C(C)(=O)OCC Chemical compound C([C@H](O)[C@@H](O)C(=O)O)(=O)O.C(C)(=O)OCC DLXLXJXLPPYFLA-ZVGUSBNCSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102000018682 Interleukin Receptor Common gamma Subunit Human genes 0.000 description 2
- 108010066719 Interleukin Receptor Common gamma Subunit Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 101150009057 JAK2 gene Proteins 0.000 description 2
- 108010024121 Janus Kinases Proteins 0.000 description 2
- 102000015617 Janus Kinases Human genes 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 102000038030 PI3Ks Human genes 0.000 description 2
- 108091007960 PI3Ks Proteins 0.000 description 2
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 2
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 2
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 2
- JBQLQIMCKFDOHK-UHFFFAOYSA-N Stephanol Natural products CC(O)C1(O)CCC2(O)C3(O)CC=C4CC(O)CCC4(C)C3C(O)C(O)C12C JBQLQIMCKFDOHK-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000012490 blank solution Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- LBJNMUFDOHXDFG-UHFFFAOYSA-N copper;hydrate Chemical compound O.[Cu].[Cu] LBJNMUFDOHXDFG-UHFFFAOYSA-N 0.000 description 2
- 238000003795 desorption Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- CXISHPLSAAGNQA-UHFFFAOYSA-N ethyl acetate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound CCOC(C)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O CXISHPLSAAGNQA-UHFFFAOYSA-N 0.000 description 2
- UACSTJFVSYFIPA-UHFFFAOYSA-N ethyl acetate;hydrobromide Chemical compound Br.CCOC(C)=O UACSTJFVSYFIPA-UHFFFAOYSA-N 0.000 description 2
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 2
- 238000010812 external standard method Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- CBKHIMUFQXZHDD-UHFFFAOYSA-N methanesulfonic acid;propan-2-one Chemical compound CC(C)=O.CS(O)(=O)=O CBKHIMUFQXZHDD-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- ZPLUZNXSYCCJOE-UHFFFAOYSA-N phosphoric acid;propan-2-one Chemical compound CC(C)=O.OP(O)(O)=O ZPLUZNXSYCCJOE-UHFFFAOYSA-N 0.000 description 2
- YVGLSUJNDXBZBM-UHFFFAOYSA-N propan-2-one;hydrobromide Chemical compound Br.CC(C)=O YVGLSUJNDXBZBM-UHFFFAOYSA-N 0.000 description 2
- LBZIXWRZFXPLJU-UHFFFAOYSA-N propan-2-one;sulfuric acid Chemical compound CC(C)=O.OS(O)(=O)=O LBZIXWRZFXPLJU-UHFFFAOYSA-N 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000011535 reaction buffer Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000006104 solid solution Substances 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 239000012086 standard solution Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001502 supplementing effect Effects 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- HGNXHCJAXKQSOQ-UHFFFAOYSA-N 12-oxa-3,5,8-triazatricyclo[7.3.0.02,6]dodeca-1,3,6,8,10-pentaene Chemical class N1C=NC=2C1=C1C(=NC=2)C=CO1 HGNXHCJAXKQSOQ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- KYARBIJYVGJZLB-UHFFFAOYSA-N 7-amino-4-hydroxy-2-naphthalenesulfonic acid Chemical compound OC1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 KYARBIJYVGJZLB-UHFFFAOYSA-N 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 1
- 102000010781 Interleukin-6 Receptors Human genes 0.000 description 1
- 108010038501 Interleukin-6 Receptors Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108091008611 Protein Kinase B Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102000005765 Proto-Oncogene Proteins c-akt Human genes 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 1
- 101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 1
- 102000036693 Thrombopoietin Human genes 0.000 description 1
- 108010041111 Thrombopoietin Proteins 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229940123371 Tyrosine kinase 2 inhibitor Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000035578 autophosphorylation Effects 0.000 description 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 238000012864 cross contamination Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 239000003517 fume Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 101150079478 jak1 gene Proteins 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical class [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000012430 stability testing Methods 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Images
Classifications
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4155—1,2-Diazoles non 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
- C07D491/147—Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
一种作为选择性Jak1/TYK2激酶抑制剂的化合物2‑[(2R,5S)‑5‑[2‑甲基呋喃并[3,2‑b]咪唑并[4,5‑d]吡啶‑1‑基]四氢吡喃‑2‑基]乙腈的合成方法，该化合物以7‑氯‑6‑硝基呋喃并[3,2‑b]吡啶为起始原料，经亲核取代、钯炭还原、环合反应制备得到。该合成方法反应条件温和、产品收率高、纯度高、适合工业化生产。一种涉及该化合物的晶型、其盐的晶型以及它们的制备方法，该化合物的晶型、其盐的晶型具有良好的理化性质，适合药物开发。
Description
PCT国内申请，说明书已公开。
Claims (77)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910490711 | 2019-06-06 | ||
| CN2019104907114 | 2019-06-06 | ||
| PCT/CN2020/088122 WO2020244349A1 (zh) | 2019-06-06 | 2020-04-30 | 呋喃并咪唑并吡啶类化合物的合成方法、多晶型物、及盐的多晶型物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114007606A true CN114007606A (zh) | 2022-02-01 |
| CN114007606B CN114007606B (zh) | 2023-12-08 |
Family
ID=73652741
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202080037087.3A Active CN114007606B (zh) | 2019-06-06 | 2020-04-30 | 呋喃并咪唑并吡啶类化合物的合成方法、多晶型物、及盐的多晶型物 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20220242873A1 (zh) |
| EP (3) | EP3981398A4 (zh) |
| JP (1) | JP2022537919A (zh) |
| KR (1) | KR20220017990A (zh) |
| CN (1) | CN114007606B (zh) |
| AU (1) | AU2020287139A1 (zh) |
| BR (1) | BR112021024530A2 (zh) |
| CA (1) | CA3142629A1 (zh) |
| EA (1) | EA202192871A1 (zh) |
| IL (1) | IL288349A (zh) |
| MX (1) | MX2021014320A (zh) |
| WO (1) | WO2020244349A1 (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4419101A1 (en) * | 2021-09-13 | 2024-08-28 | Hangzhou Highlightll Pharmaceutical Co., Ltd. | Methods of treating cns disorders |
| CN114213424B (zh) * | 2021-12-30 | 2023-05-26 | 杭州高光制药有限公司 | 一种呋喃[3，2-b]并吡啶衍生物的合成方法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104918945A (zh) * | 2012-11-01 | 2015-09-16 | 因赛特公司 | 作为jak抑制剂的三环稠合噻吩衍生物 |
| CN106687462A (zh) * | 2014-04-30 | 2017-05-17 | 因赛特公司 | Jak1抑制剂的制备方法以及其新形式 |
| CN108366994A (zh) * | 2016-10-03 | 2018-08-03 | 梁从新 | 新型Jak1选择性抑制剂及其用途 |
-
2020
- 2020-04-30 WO PCT/CN2020/088122 patent/WO2020244349A1/zh active Application Filing
- 2020-04-30 US US17/615,437 patent/US20220242873A1/en active Pending
- 2020-04-30 EP EP20817954.9A patent/EP3981398A4/en active Pending
- 2020-04-30 EA EA202192871A patent/EA202192871A1/ru unknown
- 2020-04-30 BR BR112021024530A patent/BR112021024530A2/pt unknown
- 2020-04-30 EP EP24173874.9A patent/EP4393492A3/en active Pending
- 2020-04-30 MX MX2021014320A patent/MX2021014320A/es unknown
- 2020-04-30 CA CA3142629A patent/CA3142629A1/en active Pending
- 2020-04-30 JP JP2021572486A patent/JP2022537919A/ja active Pending
- 2020-04-30 EP EP24173596.8A patent/EP4385511A3/en active Pending
- 2020-04-30 AU AU2020287139A patent/AU2020287139A1/en active Pending
- 2020-04-30 CN CN202080037087.3A patent/CN114007606B/zh active Active
- 2020-04-30 KR KR1020227000070A patent/KR20220017990A/ko unknown
-
2021
- 2021-11-24 IL IL288349A patent/IL288349A/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104918945A (zh) * | 2012-11-01 | 2015-09-16 | 因赛特公司 | 作为jak抑制剂的三环稠合噻吩衍生物 |
| CN106687462A (zh) * | 2014-04-30 | 2017-05-17 | 因赛特公司 | Jak1抑制剂的制备方法以及其新形式 |
| CN108366994A (zh) * | 2016-10-03 | 2018-08-03 | 梁从新 | 新型Jak1选择性抑制剂及其用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP4385511A3 (en) | 2024-08-07 |
| AU2020287139A2 (en) | 2022-01-13 |
| EP4393492A2 (en) | 2024-07-03 |
| EP4393492A3 (en) | 2024-08-07 |
| EA202192871A1 (ru) | 2022-03-22 |
| CA3142629A1 (en) | 2020-12-10 |
| IL288349A (en) | 2022-01-01 |
| EP4385511A2 (en) | 2024-06-19 |
| WO2020244349A1 (zh) | 2020-12-10 |
| CN114007606B (zh) | 2023-12-08 |
| KR20220017990A (ko) | 2022-02-14 |
| BR112021024530A2 (pt) | 2022-01-18 |
| JP2022537919A (ja) | 2022-08-31 |
| MX2021014320A (es) | 2022-02-21 |
| US20220242873A1 (en) | 2022-08-04 |
| EP3981398A4 (en) | 2023-03-15 |
| EP3981398A1 (en) | 2022-04-13 |
| AU2020287139A1 (en) | 2022-01-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2023089169A (ja) | フロイミダゾピリジン化合物の合成方法、フロイミダゾピリジン化合物の結晶形態およびそれらの塩の結晶形態 | |
| CN114007606B (zh) | 呋喃并咪唑并吡啶类化合物的合成方法、多晶型物、及盐的多晶型物 | |
| CN108602772A (zh) | 1-(5-(2,4-二氟苯基)-1-((3-氟苯基)磺酰基)-4-甲氧基-1h-吡咯-3-基)-n-甲基甲胺盐新晶型 | |
| CN114746412A (zh) | Kd-025的新晶型及其制备方法 | |
| JP7351061B2 (ja) | 縮合環ピリミジン系化合物の塩、結晶形並びにその製造方法と使用 | |
| CN111511743A (zh) | 结晶的利拉利汀中间体及利拉利汀的制备方法 | |
| JP2023543080A (ja) | ピロロ複素環系誘導体の結晶及びその製造方法 | |
| CN111094272B (zh) | 一种otr抑制剂的可药用盐、晶型及制备方法 | |
| EA044931B1 (ru) | Способ синтеза фуроимидазопиридинового соединения, полиморфного вещества и полиморфа соли | |
| EA045390B1 (ru) | Способ синтеза фуроимидазопиридинового соединения, кристаллическая форма фуроимидазопиридинового соединения и кристаллическая форма его соли | |
| EA047316B1 (ru) | Способ синтеза фуроимидазопиридинового соединения, кристаллическая форма фуроимидазопиридинового соединения и кристаллическая форма его соли | |
| CN114773211B (zh) | 一种葡甲胺盐的晶型、其制备方法及应用 | |
| CN111902406B (zh) | 氮杂双环基取代的三唑类衍生物的可药用盐、晶型及制备方法 | |
| CN114181211B (zh) | 一种酮咯酸与苯甲酰胺共晶体及其制备方法 | |
| WO2023174300A1 (zh) | Btk抑制剂的晶型及其酸式盐和其酸式盐的晶型 | |
| CN115232124A (zh) | 一种atx抑制剂的结晶形式及其制备方法 | |
| CN116514796A (zh) | 3CLpro蛋白酶抑制剂的盐、晶型及其制备方法 | |
| CN117642405A (zh) | 一种三环四氢异喹啉类衍生物的盐型 | |
| CN117586282A (zh) | 一种稠合四环类衍生物的可药用盐、晶型及制备方法 | |
| TW202333694A (zh) | 稠環衍生物的晶型、其製備方法及其應用 | |
| CN113461662A (zh) | 羟哌吡酮可药用盐的新晶型及其制备方法 | |
| CN118184638A (zh) | 盐型的glp-1受体激动剂、其晶型和制备方法及其药物组合物和用途 | |
| CN117756819A (zh) | Tyk2抑制剂的晶型及其制备 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 40062038 Country of ref document: HK |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |