TWI803511B - 嗎啉基吡啶酮化合物 - Google Patents

Info

Publication number

TWI803511B

TWI803511B TW107129499A TW107129499A TWI803511B TW I803511 B TWI803511 B TW I803511B TW 107129499 A TW107129499 A TW 107129499A TW 107129499 A TW107129499 A TW 107129499A TW I803511 B TWI803511 B TW I803511B

Authority

TW

Taiwan

Prior art keywords

trifluoromethyl

compound

cancer

pharmaceutically acceptable

pyridin

Prior art date

2017-08-23

Links

• Espacenet
• Global Dossier
• Discuss

• NMVVTUFCOTZTMF-UHFFFAOYSA-N 3-morpholin-4-yl-1h-pyridin-2-one Chemical class O=C1NC=CC=C1N1CCOCC1 NMVVTUFCOTZTMF-UHFFFAOYSA-N 0.000 title abstract description 3
• 150000001875 compounds Chemical class 0.000 claims abstract description 122
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 41
• 201000011510 cancer Diseases 0.000 claims abstract description 27
• 201000010099 disease Diseases 0.000 claims abstract description 16
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
• 238000011282 treatment Methods 0.000 claims abstract description 12
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 9
• 208000036142 Viral infection Diseases 0.000 claims abstract description 7
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 7
• 230000009385 viral infection Effects 0.000 claims abstract description 7
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 6
• 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 6
• 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 6
• 150000003839 salts Chemical class 0.000 claims description 48
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
• 239000003814 drug Substances 0.000 claims description 21
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 14
• 239000001257 hydrogen Substances 0.000 claims description 10
• 229910052739 hydrogen Inorganic materials 0.000 claims description 10
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
• 206010021143 Hypoxia Diseases 0.000 claims description 9
• 238000002360 preparation method Methods 0.000 claims description 9
• 206010006187 Breast cancer Diseases 0.000 claims description 8
• 208000026310 Breast neoplasm Diseases 0.000 claims description 8
• 229910052736 halogen Inorganic materials 0.000 claims description 8
• 230000001146 hypoxic effect Effects 0.000 claims description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
• 239000003085 diluting agent Substances 0.000 claims description 7
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 6
• 206010005003 Bladder cancer Diseases 0.000 claims description 6
• 206010008342 Cervix carcinoma Diseases 0.000 claims description 6
• 206010009944 Colon cancer Diseases 0.000 claims description 6
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 6
• 102000004190 Enzymes Human genes 0.000 claims description 6
• 108090000790 Enzymes Proteins 0.000 claims description 6
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
• 208000032612 Glial tumor Diseases 0.000 claims description 6
• 206010018338 Glioma Diseases 0.000 claims description 6
• 208000008839 Kidney Neoplasms Diseases 0.000 claims description 6
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 6
• 206010025323 Lymphomas Diseases 0.000 claims description 6
• 206010033128 Ovarian cancer Diseases 0.000 claims description 6
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 6
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 6
• 206010060862 Prostate cancer Diseases 0.000 claims description 6
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 6
• 206010038389 Renal cancer Diseases 0.000 claims description 6
• 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims description 6
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 6
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 6
• 239000002246 antineoplastic agent Substances 0.000 claims description 6
• 201000010881 cervical cancer Diseases 0.000 claims description 6
• 229910052731 fluorine Inorganic materials 0.000 claims description 6
• 239000011737 fluorine Substances 0.000 claims description 6
• 201000010982 kidney cancer Diseases 0.000 claims description 6
• 208000032839 leukemia Diseases 0.000 claims description 6
• 201000007270 liver cancer Diseases 0.000 claims description 6
• 208000014018 liver neoplasm Diseases 0.000 claims description 6
• 201000005202 lung cancer Diseases 0.000 claims description 6
• 208000020816 lung neoplasm Diseases 0.000 claims description 6
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 6
• 201000002528 pancreatic cancer Diseases 0.000 claims description 6
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• 208000022679 triple-negative breast carcinoma Diseases 0.000 claims description 6
• 201000005112 urinary bladder cancer Diseases 0.000 claims description 6
• 150000002367 halogens Chemical class 0.000 claims description 5
• 201000001441 melanoma Diseases 0.000 claims description 5
• KIRRPVVLWZDEOM-UHFFFAOYSA-N 4-(3-methylmorpholin-4-yl)-6-[4-(2-methylpyrazol-3-yl)sulfonyl-2-(trifluoromethyl)piperazin-1-yl]-1H-pyridin-2-one Chemical compound CC1N(CCOC1)C1=CC(NC(=C1)N1C(CN(CC1)S(=O)(=O)C=1N(N=CC=1)C)C(F)(F)F)=O KIRRPVVLWZDEOM-UHFFFAOYSA-N 0.000 claims description 4
• YAGDPINTXNUJFA-UHFFFAOYSA-N 4-(3-methylmorpholin-4-yl)-6-[4-(oxolan-3-ylsulfonyl)-2-(trifluoromethyl)piperazin-1-yl]-1H-pyridin-2-one Chemical compound CC1N(CCOC1)C1=CC(NC(=C1)N1C(CN(CC1)S(=O)(=O)C1COCC1)C(F)(F)F)=O YAGDPINTXNUJFA-UHFFFAOYSA-N 0.000 claims description 4
• LTTGFQYAQYEYHW-UHFFFAOYSA-N 4-(3-methylmorpholin-4-yl)-6-[4-methylsulfonyl-2-(trifluoromethyl)piperazin-1-yl]-1H-pyridin-2-one Chemical compound CC1N(CCOC1)C1=CC(NC(=C1)N1C(CN(CC1)S(=O)(=O)C)C(F)(F)F)=O LTTGFQYAQYEYHW-UHFFFAOYSA-N 0.000 claims description 4
• AYEISBMTIDMDIW-UHFFFAOYSA-N 6-[4-(5-fluoropyridin-3-yl)sulfonyl-2-(trifluoromethyl)piperazin-1-yl]-4-(3-methylmorpholin-4-yl)-1H-pyridin-2-one Chemical compound FC=1C=C(C=NC=1)S(=O)(=O)N1CC(N(CC1)C1=CC(=CC(N1)=O)N1C(COCC1)C)C(F)(F)F AYEISBMTIDMDIW-UHFFFAOYSA-N 0.000 claims description 4
• BFZZOZQOAVINFN-UHFFFAOYSA-N N,N-dimethyl-4-[4-(3-methylmorpholin-4-yl)-6-oxo-1H-pyridin-2-yl]-3-(trifluoromethyl)piperazine-1-sulfonamide Chemical compound CN(S(=O)(=O)N1CC(N(CC1)C=1NC(C=C(C=1)N1C(COCC1)C)=O)C(F)(F)F)C BFZZOZQOAVINFN-UHFFFAOYSA-N 0.000 claims description 4
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
• 238000001959 radiotherapy Methods 0.000 claims description 4
• FKHNSGHHGRJGMU-UHFFFAOYSA-N 4-(3-methylmorpholin-4-yl)-6-[4-pyrrolidin-1-ylsulfonyl-2-(trifluoromethyl)piperazin-1-yl]-1H-pyridin-2-one Chemical compound CC1N(CCOC1)C1=CC(NC(=C1)N1C(CN(CC1)S(=O)(=O)N1CCCC1)C(F)(F)F)=O FKHNSGHHGRJGMU-UHFFFAOYSA-N 0.000 claims description 3
• LMMZDANJUDIECD-UHFFFAOYSA-N 6-[4-(4-fluorophenyl)sulfonyl-2-(trifluoromethyl)piperazin-1-yl]-4-(3-methylmorpholin-4-yl)-1H-pyridin-2-one Chemical compound FC1=CC=C(C=C1)S(=O)(=O)N1CC(N(CC1)C1=CC(=CC(N1)=O)N1C(COCC1)C)C(F)(F)F LMMZDANJUDIECD-UHFFFAOYSA-N 0.000 claims description 3
• MCOXRIXWEFCOLO-UHFFFAOYSA-N 6-[4-[(4-fluorophenyl)methylsulfonyl]-2-(trifluoromethyl)piperazin-1-yl]-4-(3-methylmorpholin-4-yl)-1H-pyridin-2-one Chemical compound FC1=CC=C(C=C1)CS(=O)(=O)N1CC(N(CC1)C1=CC(=CC(N1)=O)N1C(COCC1)C)C(F)(F)F MCOXRIXWEFCOLO-UHFFFAOYSA-N 0.000 claims description 3
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
• 238000006467 substitution reaction Methods 0.000 claims description 3
• BPXSDXXWOWIEGU-UHFFFAOYSA-N 4-(3-methylmorpholin-4-yl)-6-[4-methylsulfonyl-2-(trifluoromethyl)phenyl]-1H-pyridin-2-one Chemical compound CC1N(CCOC1)C1=CC(NC(=C1)C1=C(C=C(C=C1)S(=O)(=O)C)C(F)(F)F)=O BPXSDXXWOWIEGU-UHFFFAOYSA-N 0.000 claims description 2
• VGAYOERTTXJDOP-UHFFFAOYSA-N 4-(3-methylmorpholin-4-yl)-6-[4-piperidin-1-ylsulfonyl-2-(trifluoromethyl)piperazin-1-yl]-1H-pyridin-2-one Chemical compound CC1N(CCOC1)C1=CC(NC(=C1)N1C(CN(CC1)S(=O)(=O)N1CCCCC1)C(F)(F)F)=O VGAYOERTTXJDOP-UHFFFAOYSA-N 0.000 claims description 2
• YRXRLABGSILYCG-UHFFFAOYSA-N 6-[4-(1,2-dimethylimidazol-4-yl)sulfonyl-2-(trifluoromethyl)piperazin-1-yl]-4-(3-methylmorpholin-4-yl)-1H-pyridin-2-one Chemical compound CN1C(=NC(=C1)S(=O)(=O)N1CC(N(CC1)C1=CC(=CC(N1)=O)N1C(COCC1)C)C(F)(F)F)C YRXRLABGSILYCG-UHFFFAOYSA-N 0.000 claims description 2
• JAVRYPHODLVYTQ-UHFFFAOYSA-N 6-[4-(1-methylcyclopropyl)sulfonyl-2-(trifluoromethyl)piperazin-1-yl]-4-(3-methylmorpholin-4-yl)-1H-pyridin-2-one Chemical compound CC1(CC1)S(=O)(=O)N1CC(N(CC1)C1=CC(=CC(N1)=O)N1C(COCC1)C)C(F)(F)F JAVRYPHODLVYTQ-UHFFFAOYSA-N 0.000 claims description 2
• 241000196324 Embryophyta Species 0.000 claims description 2
• 102000014150 Interferons Human genes 0.000 claims description 2
• 108010050904 Interferons Proteins 0.000 claims description 2
• 241000009298 Trigla lyra Species 0.000 claims description 2
• 239000002168 alkylating agent Substances 0.000 claims description 2
• 229940100198 alkylating agent Drugs 0.000 claims description 2
• 239000003242 anti bacterial agent Substances 0.000 claims description 2
• 230000001093 anti-cancer Effects 0.000 claims description 2
• 230000000340 anti-metabolite Effects 0.000 claims description 2
• 229940088710 antibiotic agent Drugs 0.000 claims description 2
• 229940100197 antimetabolite Drugs 0.000 claims description 2
• 239000002256 antimetabolite Substances 0.000 claims description 2
• VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical class C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 2
• 229940088597 hormone Drugs 0.000 claims description 2
• 239000005556 hormone Substances 0.000 claims description 2
• 239000003667 hormone antagonist Substances 0.000 claims description 2
• 229940079322 interferon Drugs 0.000 claims description 2
• 230000010468 interferon response Effects 0.000 claims description 2
• 229910052697 platinum Inorganic materials 0.000 claims description 2
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims description 2
• 239000005483 tyrosine kinase inhibitor Substances 0.000 claims description 2
• YLNDUJZNLZBUIQ-UHFFFAOYSA-N 6-[4-(2-methoxyethylsulfonyl)-2-(trifluoromethyl)piperazin-1-yl]-4-(3-methylmorpholin-4-yl)-1H-pyridin-2-one Chemical compound COCCS(=O)(=O)N1CC(N(CC1)C1=CC(=CC(N1)=O)N1C(COCC1)C)C(F)(F)F YLNDUJZNLZBUIQ-UHFFFAOYSA-N 0.000 claims 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
• 230000005784 autoimmunity Effects 0.000 claims 1
• 230000008512 biological response Effects 0.000 claims 1
• 125000001475 halogen functional group Chemical group 0.000 claims 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
• 230000004770 neurodegeneration Effects 0.000 claims 1
• 201000003733 ovarian melanoma Diseases 0.000 claims 1
• 108091008020 response regulators Proteins 0.000 claims 1
• 208000012201 sexual and gender identity disease Diseases 0.000 claims 1
• 208000015891 sexual disease Diseases 0.000 claims 1
• XPDWGBQVDMORPB-UHFFFAOYSA-N trifluoromethane acid Natural products FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 13
• 239000000203 mixture Substances 0.000 description 46
• 239000000047 product Substances 0.000 description 34
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 32
• 239000007787 solid Substances 0.000 description 32
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 25
• 235000002639 sodium chloride Nutrition 0.000 description 24
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
• 238000006243 chemical reaction Methods 0.000 description 23
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
• 125000004432 carbon atom Chemical group C* 0.000 description 18
• 239000004480 active ingredient Substances 0.000 description 17
• 125000005843 halogen group Chemical group 0.000 description 17
• 235000019439 ethyl acetate Nutrition 0.000 description 16
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
• -1 methoxy, dimethylamino Chemical group 0.000 description 15
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
• 102100038329 Phosphatidylinositol 3-kinase catalytic subunit type 3 Human genes 0.000 description 14
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
• 101000605630 Homo sapiens Phosphatidylinositol 3-kinase catalytic subunit type 3 Proteins 0.000 description 13
• 239000002585 base Substances 0.000 description 13
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 13
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
• 210000004027 cell Anatomy 0.000 description 11
• 238000003556 assay Methods 0.000 description 10
• 230000004900 autophagic degradation Effects 0.000 description 10
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 9
• 239000012267 brine Substances 0.000 description 9
• 125000001153 fluoro group Chemical group F* 0.000 description 9
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 9
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
• 239000002904 solvent Substances 0.000 description 9
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
• 239000000741 silica gel Substances 0.000 description 8
• 229910002027 silica gel Inorganic materials 0.000 description 8
• 239000003826 tablet Substances 0.000 description 8
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
• 239000007832 Na2SO4 Substances 0.000 description 7
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• 150000002430 hydrocarbons Chemical group 0.000 description 7
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• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
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• 229930195734 saturated hydrocarbon Natural products 0.000 description 7
• 229910052938 sodium sulfate Inorganic materials 0.000 description 7
• 235000011152 sodium sulphate Nutrition 0.000 description 7
• 239000000243 solution Substances 0.000 description 7
• MPTSNJXCLCPMAF-IURRXHLWSA-N (3R)-3-methyl-4-[2-[(2-methylpropan-2-yl)oxy]-6-[4-methylsulfonyl-2-(trifluoromethyl)piperazin-1-yl]pyridin-4-yl]morpholine Chemical compound C(C)(C)(C)OC1=NC(=CC(=C1)N1[C@@H](COCC1)C)N1C(CN(CC1)S(=O)(=O)C)C(F)(F)F MPTSNJXCLCPMAF-IURRXHLWSA-N 0.000 description 6
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-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
• 239000002253 acid Substances 0.000 description 6
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
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• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 5
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
• 235000011054 acetic acid Nutrition 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 239000000460 chlorine Substances 0.000 description 5
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• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
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• KKDYXLUSGMODIB-SNVBAGLBSA-N (3R)-4-[2-chloro-6-[(2-methylpropan-2-yl)oxy]pyridin-4-yl]-3-methylmorpholine Chemical compound C(C)(C)(C)OC1=NC(=CC(=C1)N1[C@@H](COCC1)C)Cl KKDYXLUSGMODIB-SNVBAGLBSA-N 0.000 description 4
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 4
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• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 229910052757 nitrogen Inorganic materials 0.000 description 4
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 4
• 150000003905 phosphatidylinositols Chemical class 0.000 description 4
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
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• 125000004076 pyridyl group Chemical group 0.000 description 4
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 4
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 4
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
• 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 description 3
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• FMDWPLJEKVUGTC-UHFFFAOYSA-N 1-methylcyclopropane-1-sulfonyl chloride Chemical compound ClS(=O)(=O)C1(C)CC1 FMDWPLJEKVUGTC-UHFFFAOYSA-N 0.000 description 3
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• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
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