KR20230165238A - 비시클릭 케톤 화합물 제조 공정 - Google Patents
비시클릭 케톤 화합물 제조 공정 Download PDFInfo
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- KR20230165238A KR20230165238A KR1020237033599A KR20237033599A KR20230165238A KR 20230165238 A KR20230165238 A KR 20230165238A KR 1020237033599 A KR1020237033599 A KR 1020237033599A KR 20237033599 A KR20237033599 A KR 20237033599A KR 20230165238 A KR20230165238 A KR 20230165238A
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- -1 Bicyclic Ketone Compound Chemical class 0.000 title claims abstract description 289
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 22
- 150000001875 compounds Chemical class 0.000 claims abstract description 175
- 238000000034 method Methods 0.000 claims abstract description 160
- 230000008569 process Effects 0.000 claims abstract description 142
- 150000003839 salts Chemical class 0.000 claims abstract description 127
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 140
- 239000002253 acid Substances 0.000 claims description 97
- 239000000203 mixture Substances 0.000 claims description 72
- 239000000654 additive Substances 0.000 claims description 60
- 230000000996 additive effect Effects 0.000 claims description 53
- 101001110310 Lentilactobacillus kefiri NADP-dependent (R)-specific alcohol dehydrogenase Proteins 0.000 claims description 46
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 45
- 238000006243 chemical reaction Methods 0.000 claims description 41
- 239000002904 solvent Substances 0.000 claims description 41
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 36
- 229910052799 carbon Inorganic materials 0.000 claims description 33
- 239000003960 organic solvent Substances 0.000 claims description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
- 238000002360 preparation method Methods 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 27
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 25
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 23
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 20
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 20
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 239000005515 coenzyme Substances 0.000 claims description 18
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 18
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical group 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 229910052731 fluorine Inorganic materials 0.000 claims description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical group C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 12
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 claims description 12
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical group COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical group CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 235000019253 formic acid Nutrition 0.000 claims description 10
- 230000002140 halogenating effect Effects 0.000 claims description 10
- 150000003333 secondary alcohols Chemical class 0.000 claims description 10
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 150000007530 organic bases Chemical class 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 9
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 8
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 8
- 108010050375 Glucose 1-Dehydrogenase Proteins 0.000 claims description 8
- 125000006242 amine protecting group Chemical group 0.000 claims description 8
- 150000007524 organic acids Chemical class 0.000 claims description 8
- LUYQYZLEHLTPBH-UHFFFAOYSA-N perfluorobutanesulfonyl fluoride Chemical group FC(F)(F)C(F)(F)C(F)(F)C(F)(F)S(F)(=O)=O LUYQYZLEHLTPBH-UHFFFAOYSA-N 0.000 claims description 7
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical group Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 6
- 239000002841 Lewis acid Substances 0.000 claims description 6
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical group NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 claims description 6
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 claims description 6
- 101710088580 Stromal cell-derived factor 1 Proteins 0.000 claims description 6
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 6
- 150000007517 lewis acids Chemical class 0.000 claims description 6
- FCFXLXGZHDHJLB-UHFFFAOYSA-N pyridine-2-sulfonyl fluoride Chemical compound FS(=O)(=O)C1=CC=CC=N1 FCFXLXGZHDHJLB-UHFFFAOYSA-N 0.000 claims description 6
- 230000000707 stereoselective effect Effects 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 239000007822 coupling agent Substances 0.000 claims description 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- IKGLACJFEHSFNN-UHFFFAOYSA-N hydron;triethylazanium;trifluoride Chemical group F.F.F.CCN(CC)CC IKGLACJFEHSFNN-UHFFFAOYSA-N 0.000 claims description 4
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 claims 2
- 239000000243 solution Substances 0.000 description 59
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical group CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 40
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 35
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
- 125000004122 cyclic group Chemical group 0.000 description 31
- 239000003153 chemical reaction reagent Substances 0.000 description 29
- 239000007787 solid Substances 0.000 description 28
- 239000000460 chlorine Substances 0.000 description 27
- 239000000706 filtrate Substances 0.000 description 26
- 239000000047 product Substances 0.000 description 26
- 238000004128 high performance liquid chromatography Methods 0.000 description 25
- 230000015572 biosynthetic process Effects 0.000 description 24
- 238000005481 NMR spectroscopy Methods 0.000 description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 23
- 239000011521 glass Substances 0.000 description 23
- 238000003756 stirring Methods 0.000 description 22
- 102000004190 Enzymes Human genes 0.000 description 19
- 108090000790 Enzymes Proteins 0.000 description 19
- 229910052757 nitrogen Inorganic materials 0.000 description 19
- 238000006722 reduction reaction Methods 0.000 description 18
- 102100022501 Receptor-interacting serine/threonine-protein kinase 1 Human genes 0.000 description 17
- 101710138589 Receptor-interacting serine/threonine-protein kinase 1 Proteins 0.000 description 17
- 239000000543 intermediate Substances 0.000 description 17
- 230000009467 reduction Effects 0.000 description 17
- 239000008346 aqueous phase Substances 0.000 description 16
- HEWAMPODKFTBJZ-LLVKDONJSA-N ethyl (2r)-2-hydroxy-4-oxo-4-phenylbutanoate Chemical compound CCOC(=O)[C@H](O)CC(=O)C1=CC=CC=C1 HEWAMPODKFTBJZ-LLVKDONJSA-N 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 16
- 125000001072 heteroaryl group Chemical group 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- XVZCIIVQCIBTGQ-DTWKUNHWSA-N NN([C@@H](C[C@H]1O)C2=CC=CC=C2)C1=O Chemical compound NN([C@@H](C[C@H]1O)C2=CC=CC=C2)C1=O XVZCIIVQCIBTGQ-DTWKUNHWSA-N 0.000 description 14
- 239000002585 base Substances 0.000 description 14
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 14
- 229940002612 prodrug Drugs 0.000 description 14
- 239000000651 prodrug Substances 0.000 description 14
- 125000004429 atom Chemical group 0.000 description 13
- ROLJNUSAWXADTD-UHFFFAOYSA-N ethyl 2-ethoxy-2-iminoacetate;hydrochloride Chemical compound Cl.CCOC(=N)C(=O)OCC ROLJNUSAWXADTD-UHFFFAOYSA-N 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- 229910052717 sulfur Inorganic materials 0.000 description 13
- XJLXINKUBYWONI-NNYOXOHSSA-O NADP(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-NNYOXOHSSA-O 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- DACSQAXYCBLDNU-QFGUUYLXSA-N CCOC([C@@H](C/C(\C1=CC=CC=C1)=N\NC(OC(C)(C)C)=O)O)=O Chemical compound CCOC([C@@H](C/C(\C1=CC=CC=C1)=N\NC(OC(C)(C)C)=O)O)=O DACSQAXYCBLDNU-QFGUUYLXSA-N 0.000 description 11
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- 235000011054 acetic acid Nutrition 0.000 description 10
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- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 9
- LMXPZWQVDDSYHH-RYUDHWBXSA-N F[C@H]1C[C@H](N2N=C(N=C12)C(=O)C1CC1)C1=CC=CC=C1 Chemical group F[C@H]1C[C@H](N2N=C(N=C12)C(=O)C1CC1)C1=CC=CC=C1 LMXPZWQVDDSYHH-RYUDHWBXSA-N 0.000 description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 125000004430 oxygen atom Chemical group O* 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 8
- 230000001640 apoptogenic effect Effects 0.000 description 8
- 230000001580 bacterial effect Effects 0.000 description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical group CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 8
- 230000002255 enzymatic effect Effects 0.000 description 8
- YMBMCMOZIGSBOA-UHFFFAOYSA-N ethyl 2-amino-2-sulfanylideneacetate Chemical group CCOC(=O)C(N)=S YMBMCMOZIGSBOA-UHFFFAOYSA-N 0.000 description 8
- MSMGXWFHBSCQFB-UHFFFAOYSA-N ethyl cyanoformate Chemical compound CCOC(=O)C#N MSMGXWFHBSCQFB-UHFFFAOYSA-N 0.000 description 8
- 150000002576 ketones Chemical class 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- 239000011593 sulfur Substances 0.000 description 8
- LKNPNZKIOSOWES-UHFFFAOYSA-N triethyl 1,3,5-triazine-2,4,6-tricarboxylate Chemical compound CCOC(=O)C1=NC(C(=O)OCC)=NC(C(=O)OCC)=N1 LKNPNZKIOSOWES-UHFFFAOYSA-N 0.000 description 8
- UARJMNREPJSYHA-LLVKDONJSA-N (2r)-2-acetyloxy-4-oxo-4-phenylbutanoic acid Chemical compound CC(=O)O[C@@H](C(O)=O)CC(=O)C1=CC=CC=C1 UARJMNREPJSYHA-LLVKDONJSA-N 0.000 description 7
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 7
- XHFXKKFVUDJSPJ-UHFFFAOYSA-N methyl 3-hydroxypentanoate Chemical compound CCC(O)CC(=O)OC XHFXKKFVUDJSPJ-UHFFFAOYSA-N 0.000 description 7
- 230000017074 necrotic cell death Effects 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
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- 125000000217 alkyl group Chemical group 0.000 description 6
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- 238000004296 chiral HPLC Methods 0.000 description 6
- UVJQQYMWMAISMQ-UHFFFAOYSA-N ethyl 2,4-dioxo-4-phenylbutanoate Chemical compound CCOC(=O)C(=O)CC(=O)C1=CC=CC=C1 UVJQQYMWMAISMQ-UHFFFAOYSA-N 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
- 125000001188 haloalkyl group Chemical group 0.000 description 6
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropyl acetate Chemical compound CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 6
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- SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical compound NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 6
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- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 6
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 6
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- BJEPYKJPYRNKOW-UWTATZPHSA-N (R)-malic acid Chemical compound OC(=O)[C@H](O)CC(O)=O BJEPYKJPYRNKOW-UWTATZPHSA-N 0.000 description 5
- TXUWMXQFNYDOEZ-UHFFFAOYSA-N 5-(1H-indol-3-ylmethyl)-3-methyl-2-sulfanylidene-4-imidazolidinone Chemical compound O=C1N(C)C(=S)NC1CC1=CNC2=CC=CC=C12 TXUWMXQFNYDOEZ-UHFFFAOYSA-N 0.000 description 5
- 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 5
- IWJCFZFZUVJTHQ-QWRGUYRKSA-N CON(C)C(=O)c1nc2[C@@H](F)C[C@@H](c3ccccc3)n2n1 Chemical group CON(C)C(=O)c1nc2[C@@H](F)C[C@@H](c3ccccc3)n2n1 IWJCFZFZUVJTHQ-QWRGUYRKSA-N 0.000 description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
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- 125000004076 pyridyl group Chemical group 0.000 description 5
- 125000003003 spiro group Chemical group 0.000 description 5
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 4
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 4
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000005306 thianaphthenyl group Chemical group 0.000 description 1
- 125000005458 thianyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001166 thiolanyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 238000005829 trimerization reaction Methods 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- XLRPYZSEQKXZAA-OCAPTIKFSA-N tropane Chemical compound C1CC[C@H]2CC[C@@H]1N2C XLRPYZSEQKXZAA-OCAPTIKFSA-N 0.000 description 1
- 229930004006 tropane Natural products 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
- C07D207/50—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/62—Carboxylic acid esters
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202163170422P | 2021-04-02 | 2021-04-02 | |
| US63/170,422 | 2021-04-02 | ||
| PCT/US2022/022997 WO2022212809A1 (en) | 2021-04-02 | 2022-04-01 | Processes for making bicyclic ketone compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20230165238A true KR20230165238A (ko) | 2023-12-05 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020237033599A Pending KR20230165238A (ko) | 2021-04-02 | 2022-04-01 | 비시클릭 케톤 화합물 제조 공정 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20240034739A1 (enExample) |
| EP (1) | EP4313986A1 (enExample) |
| JP (1) | JP2024513394A (enExample) |
| KR (1) | KR20230165238A (enExample) |
| CN (1) | CN117098762A (enExample) |
| AR (1) | AR125294A1 (enExample) |
| AU (1) | AU2022246900A1 (enExample) |
| BR (1) | BR112023020229A2 (enExample) |
| CA (1) | CA3214802A1 (enExample) |
| IL (1) | IL307250A (enExample) |
| MX (1) | MX2023011482A (enExample) |
| TW (1) | TW202304921A (enExample) |
| WO (1) | WO2022212809A1 (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2026139459A1 (en) | 2024-12-23 | 2026-07-02 | Astrazeneca Ab | Heterocyclic inhibitors of ripk1 |
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| JP3155107B2 (ja) | 1993-01-12 | 2001-04-09 | ダイセル化学工業株式会社 | 光学活性４−ハロ−３−ヒドロキシ酪酸エステルの製造方法 |
| JPH08336393A (ja) | 1995-04-13 | 1996-12-24 | Mitsubishi Chem Corp | 光学活性なγ−置換−β−ヒドロキシ酪酸エステルの製造法 |
| JP3915015B2 (ja) | 1995-08-22 | 2007-05-16 | 味の素株式会社 | 光学活性２−ヒドロキシ−４−アリール酪酸またはそのエステルの製造方法 |
| CA2234913A1 (en) * | 1995-10-18 | 1997-04-24 | Paul E. Finke | Cyclopentyl tachykinin receptor antagonists |
| US5891685A (en) | 1996-06-03 | 1999-04-06 | Mitsubishi Chemical Corporation | Method for producing ester of (S)-γ-halogenated-β-hydroxybutyric acid |
| DE19857302C2 (de) | 1998-12-14 | 2000-10-26 | Forschungszentrum Juelich Gmbh | Verfahren zur enantioselektiven Reduktion von 3,5-Dioxocarbonsäuren, deren Salze und Ester |
| AU1551701A (en) | 1999-12-03 | 2001-06-12 | Kaneka Corporation | Novel carbonyl reductase, gene thereof and method of using the same |
| AU2007201854A1 (en) * | 2000-10-17 | 2007-05-17 | Merck Serono Sa | Pharmaceutically active sulfanilide derivatives |
| HUP0400261A3 (en) | 2001-03-22 | 2005-11-28 | Bristol Myers Squibb Co | Stereoselective reduction of substituted acetophenone |
| US20080050787A1 (en) | 2003-12-02 | 2008-02-28 | Hazuki Nagai | Method for Manufacturing Optically Active Tetrahydrothiophene Derivative and Method for Crystallization of Optically Active Tetrahydrothiophene-3-Ol |
| WO2006130657A2 (en) | 2005-05-31 | 2006-12-07 | Bristol-Myers Squibb Company | Stereoselective reduction process for the preparation of pyrrolotriazine compounds |
| CN101627116B (zh) | 2007-02-08 | 2013-07-10 | 科德克希思公司 | 酮还原酶及其用途 |
| JP2010070502A (ja) * | 2008-09-19 | 2010-04-02 | Daiichi Sankyo Co Ltd | 抗真菌作用トリアゾロピリジン誘導体 |
| RU2515976C2 (ru) * | 2009-02-26 | 2014-05-20 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Азотсодержащие конденсированные гетероциклические соединения и их применение в качестве ингибиторов продукции бета-амилоида |
| TWI648274B (zh) | 2013-02-15 | 2019-01-21 | 英商葛蘭素史克智慧財產發展有限公司 | 作為激酶抑制劑之雜環醯胺類 （二） |
| RU2716136C2 (ru) | 2015-07-02 | 2020-03-06 | Ф. Хоффманн-Ля Рош Аг | Бициклические лактамы и способы их применения |
| US11071721B2 (en) * | 2016-12-02 | 2021-07-27 | Genentech, Inc. | Bicyclic amide compounds and methods of use thereof |
| CN119613408A (zh) * | 2017-07-14 | 2025-03-14 | 豪夫迈·罗氏有限公司 | 二环酮化合物及其使用方法 |
| WO2019072942A1 (en) * | 2017-10-11 | 2019-04-18 | F. Hoffmann-La Roche Ag | BICYCLIC COMPOUNDS FOR USE AS INHIBITORS OF KINASE RIP1 |
| CN113302193B (zh) * | 2019-01-11 | 2026-05-29 | 豪夫迈·罗氏有限公司 | 双环吡咯并三唑酮化合物及其使用方法 |
| CN111606890A (zh) * | 2019-02-26 | 2020-09-01 | 微境生物医药科技(上海)有限公司 | 含丙烯酰基的核转运调节剂及其用途 |
-
2022
- 2022-04-01 CA CA3214802A patent/CA3214802A1/en active Pending
- 2022-04-01 AR ARP220100830A patent/AR125294A1/es unknown
- 2022-04-01 BR BR112023020229A patent/BR112023020229A2/pt unknown
- 2022-04-01 WO PCT/US2022/022997 patent/WO2022212809A1/en not_active Ceased
- 2022-04-01 MX MX2023011482A patent/MX2023011482A/es unknown
- 2022-04-01 KR KR1020237033599A patent/KR20230165238A/ko active Pending
- 2022-04-01 CN CN202280025356.3A patent/CN117098762A/zh active Pending
- 2022-04-01 IL IL307250A patent/IL307250A/en unknown
- 2022-04-01 JP JP2023560507A patent/JP2024513394A/ja active Pending
- 2022-04-01 TW TW111112842A patent/TW202304921A/zh unknown
- 2022-04-01 EP EP22718464.5A patent/EP4313986A1/en active Pending
- 2022-04-01 AU AU2022246900A patent/AU2022246900A1/en active Pending
-
2023
- 2023-10-02 US US18/479,596 patent/US20240034739A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| AU2022246900A8 (en) | 2023-09-21 |
| CA3214802A1 (en) | 2022-10-06 |
| EP4313986A1 (en) | 2024-02-07 |
| BR112023020229A2 (pt) | 2023-11-14 |
| JP2024513394A (ja) | 2024-03-25 |
| AR125294A1 (es) | 2023-07-05 |
| MX2023011482A (es) | 2023-10-03 |
| CN117098762A (zh) | 2023-11-21 |
| AU2022246900A1 (en) | 2023-09-14 |
| TW202304921A (zh) | 2023-02-01 |
| WO2022212809A1 (en) | 2022-10-06 |
| IL307250A (en) | 2023-11-01 |
| US20240034739A1 (en) | 2024-02-01 |
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