ES2873001T3 - Heterociclaminas como inhibidores de PI3K - Google Patents

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Publication number

ES2873001T3

ES2873001T3 ES18215449T ES18215449T ES2873001T3 ES 2873001 T3 ES2873001 T3 ES 2873001T3 ES 18215449 T ES18215449 T ES 18215449T ES 18215449 T ES18215449 T ES 18215449T ES 2873001 T3 ES2873001 T3 ES 2873001T3

Authority

ES

Spain

Prior art keywords

alkyl

chloro

amino

ethyl

mmol

Prior art date

2011-09-02

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.)

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• 239000012828 PI3K inhibitor Substances 0.000 title description 5
• 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 title description 5
• 239000000203 mixture Substances 0.000 claims abstract description 358
• 150000001875 compounds Chemical class 0.000 claims abstract description 280
• -1 -OH Chemical group 0.000 claims abstract description 228
• 125000005843 halogen group Chemical group 0.000 claims abstract description 107
• 238000000034 method Methods 0.000 claims abstract description 93
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 64
• 150000003839 salts Chemical class 0.000 claims abstract description 60
• 229940043355 kinase inhibitor Drugs 0.000 claims abstract description 55
• 239000003757 phosphotransferase inhibitor Substances 0.000 claims abstract description 55
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 54
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 51
• 201000010099 disease Diseases 0.000 claims abstract description 51
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 50
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 47
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 36
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract description 33
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 30
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 30
• 125000006568 (C4-C7) heterocycloalkyl group Chemical group 0.000 claims abstract description 28
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 28
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims abstract description 24
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 19
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 18
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract description 17
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 15
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 13
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 12
• 125000001424 substituent group Chemical group 0.000 claims abstract description 12
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 11
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 10
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
• 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims abstract description 9
• 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims abstract description 9
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims abstract description 9
• 239000002246 antineoplastic agent Substances 0.000 claims abstract description 9
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 9
• 229940127089 cytotoxic agent Drugs 0.000 claims abstract description 9
• 239000008177 pharmaceutical agent Substances 0.000 claims abstract description 9
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 8
• 125000006597 (C1-C3) alkylcarbonylamino group Chemical group 0.000 claims abstract description 7
• 125000006602 (C1-C3) alkylsulfonylamino group Chemical group 0.000 claims abstract description 7
• 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims abstract description 7
• WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 claims abstract description 7
• 101100335081 Mus musculus Flt3 gene Proteins 0.000 claims abstract description 7
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 7
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims abstract description 7
• 239000003018 immunosuppressive agent Substances 0.000 claims abstract description 7
• 150000003431 steroids Chemical class 0.000 claims abstract description 7
• 230000001225 therapeutic effect Effects 0.000 claims abstract description 7
• 102100037813 Focal adhesion kinase 1 Human genes 0.000 claims abstract description 6
• 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 claims abstract description 6
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims abstract description 6
• 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims abstract description 6
• 229960003444 immunosuppressant agent Drugs 0.000 claims abstract description 6
• YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims abstract description 6
• 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 claims abstract description 5
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims abstract description 5
• 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 claims abstract description 5
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims abstract description 5
• 102100036077 Serine/threonine-protein kinase pim-1 Human genes 0.000 claims abstract description 5
• 229940121363 anti-inflammatory agent Drugs 0.000 claims abstract description 5
• 239000002260 anti-inflammatory agent Substances 0.000 claims abstract description 5
• 239000000824 cytostatic agent Substances 0.000 claims abstract description 5
• 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 claims abstract description 5
• 102000009929 raf Kinases Human genes 0.000 claims abstract description 4
• 108010077182 raf Kinases Proteins 0.000 claims abstract description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 135
• 125000000217 alkyl group Chemical group 0.000 claims description 72
• 108091000080 Phosphotransferase Proteins 0.000 claims description 21
• 102000020233 phosphotransferase Human genes 0.000 claims description 21
• 238000011282 treatment Methods 0.000 claims description 21
• 206010028980 Neoplasm Diseases 0.000 claims description 16
• 229910052799 carbon Inorganic materials 0.000 claims description 14
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 14
• 201000011510 cancer Diseases 0.000 claims description 13
• 239000003112 inhibitor Substances 0.000 claims description 9
• 125000000304 alkynyl group Chemical group 0.000 claims description 8
• 206010061218 Inflammation Diseases 0.000 claims description 7
• 125000003342 alkenyl group Chemical group 0.000 claims description 7
• 230000004054 inflammatory process Effects 0.000 claims description 7
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
• 208000019693 Lung disease Diseases 0.000 claims description 5
• 208000006673 asthma Diseases 0.000 claims description 5
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 5
• 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 4
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
• 201000001320 Atherosclerosis Diseases 0.000 claims description 4
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 4
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 4
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 4
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 4
• 201000004681 Psoriasis Diseases 0.000 claims description 4
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 4
• 206010069351 acute lung injury Diseases 0.000 claims description 4
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 4
• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 4
• 206010003246 arthritis Diseases 0.000 claims description 4
• 210000004556 brain Anatomy 0.000 claims description 4
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• 208000020084 Bone disease Diseases 0.000 claims description 3
• 206010012689 Diabetic retinopathy Diseases 0.000 claims description 3
• 206010018364 Glomerulonephritis Diseases 0.000 claims description 3
• 206010020751 Hypersensitivity Diseases 0.000 claims description 3
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
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• 230000007815 allergy Effects 0.000 claims description 3
• 230000033115 angiogenesis Effects 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 230000002489 hematologic effect Effects 0.000 claims description 3
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• 201000006417 multiple sclerosis Diseases 0.000 claims description 3
• 208000037803 restenosis Diseases 0.000 claims description 3
• 210000003932 urinary bladder Anatomy 0.000 claims description 3
• ZQPDJCIXJHUERQ-QWRGUYRKSA-N (4r)-4-[3-[(1s)-1-(4-amino-3-methylpyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-fluorophenyl]pyrrolidin-2-one Chemical compound CCOC1=C([C@H](C)N2C3=NC=NC(N)=C3C(C)=N2)C=C(Cl)C(F)=C1[C@@H]1CNC(=O)C1 ZQPDJCIXJHUERQ-QWRGUYRKSA-N 0.000 claims description 2
• ZQPDJCIXJHUERQ-GHMZBOCLSA-N (4s)-4-[3-[(1r)-1-(4-amino-3-methylpyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-fluorophenyl]pyrrolidin-2-one Chemical compound CCOC1=C([C@@H](C)N2C3=NC=NC(N)=C3C(C)=N2)C=C(Cl)C(F)=C1[C@H]1CNC(=O)C1 ZQPDJCIXJHUERQ-GHMZBOCLSA-N 0.000 claims description 2
• ZQPDJCIXJHUERQ-WDEREUQCSA-N (4s)-4-[3-[(1s)-1-(4-amino-3-methylpyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-fluorophenyl]pyrrolidin-2-one Chemical compound CCOC1=C([C@H](C)N2C3=NC=NC(N)=C3C(C)=N2)C=C(Cl)C(F)=C1[C@H]1CNC(=O)C1 ZQPDJCIXJHUERQ-WDEREUQCSA-N 0.000 claims description 2
• ZQPDJCIXJHUERQ-UHFFFAOYSA-N 4-[3-[1-(4-amino-3-methylpyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-fluorophenyl]pyrrolidin-2-one Chemical compound CCOC1=C(C(C)N2C3=NC=NC(N)=C3C(C)=N2)C=C(Cl)C(F)=C1C1CNC(=O)C1 ZQPDJCIXJHUERQ-UHFFFAOYSA-N 0.000 claims description 2
• SCBCNLJYIPIGFY-UHFFFAOYSA-N 6-[3-[1-(4-amino-3-methylpyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl]morpholin-3-one Chemical compound COC1=C(C(C)N2C3=NC=NC(N)=C3C(C)=N2)C=C(Cl)C(C)=C1C1CNC(=O)CO1 SCBCNLJYIPIGFY-UHFFFAOYSA-N 0.000 claims description 2
• 208000003950 B-cell lymphoma Diseases 0.000 claims description 2
• 208000021386 Sjogren Syndrome Diseases 0.000 claims description 2
• 208000026935 allergic disease Diseases 0.000 claims description 2
• 230000002357 endometrial effect Effects 0.000 claims description 2
• 230000002496 gastric effect Effects 0.000 claims description 2
• 125000001188 haloalkyl group Chemical group 0.000 claims description 2
• 210000004072 lung Anatomy 0.000 claims description 2
• 206010025135 lupus erythematosus Diseases 0.000 claims description 2
• 206010028417 myasthenia gravis Diseases 0.000 claims description 2
• 201000008482 osteoarthritis Diseases 0.000 claims description 2
• 210000001672 ovary Anatomy 0.000 claims description 2
• 210000003491 skin Anatomy 0.000 claims description 2
• 210000004291 uterus Anatomy 0.000 claims description 2
• ZQPDJCIXJHUERQ-MNOVXSKESA-N (4r)-4-[3-[(1r)-1-(4-amino-3-methylpyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-fluorophenyl]pyrrolidin-2-one Chemical compound CCOC1=C([C@@H](C)N2C3=NC=NC(N)=C3C(C)=N2)C=C(Cl)C(F)=C1[C@@H]1CNC(=O)C1 ZQPDJCIXJHUERQ-MNOVXSKESA-N 0.000 claims 1
• 206010020880 Hypertrophy Diseases 0.000 claims 1
• 125000004949 alkyl amino carbonyl amino group Chemical group 0.000 claims 1
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims 1
• 125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 claims 1
• 210000000496 pancreas Anatomy 0.000 claims 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 60
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 47
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract description 33
• 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 abstract description 26
• 125000006601 (C1-C3) alkylcarbamyl group Chemical group 0.000 abstract description 16
• 125000004093 cyano group Chemical group *C#N 0.000 abstract description 13
• 125000006599 (C1-C3) alkylaminocarbonylamino group Chemical group 0.000 abstract description 6
• 125000006594 (C1-C3) alkylsulfony group Chemical group 0.000 abstract description 6
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract description 6
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 abstract description 6
• 125000006592 (C2-C3) alkenyl group Chemical group 0.000 abstract description 6
• 125000006593 (C2-C3) alkynyl group Chemical group 0.000 abstract description 6
• 101100310920 Caenorhabditis elegans sra-2 gene Proteins 0.000 abstract description 5
• 125000006595 (C1-C3) alkylsulfinyl group Chemical group 0.000 abstract description 4
• 108091008605 VEGF receptors Proteins 0.000 abstract description 4
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 abstract description 4
• 125000006598 aminocarbonylamino group Chemical group 0.000 abstract description 4
• 125000000446 sulfanediyl group Chemical group *S* 0.000 abstract description 2
• 125000004966 cyanoalkyl group Chemical group 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 216
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• 239000000047 product Substances 0.000 description 205
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• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 167
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 150
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
• 229910052721 tungsten Inorganic materials 0.000 description 90
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 89
• 239000000243 solution Substances 0.000 description 81
• 238000006243 chemical reaction Methods 0.000 description 80
• 235000019439 ethyl acetate Nutrition 0.000 description 78
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 70
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 69
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 67
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 65
• 239000002585 base Substances 0.000 description 56
• 125000004432 carbon atom Chemical group C* 0.000 description 54
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 52
• 108091007960 PI3Ks Proteins 0.000 description 51
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• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 47
• 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 46
• 150000002576 ketones Chemical class 0.000 description 44
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 42
• 239000012044 organic layer Substances 0.000 description 41
• 238000004007 reversed phase HPLC Methods 0.000 description 38
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• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 37
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 37
• 239000012267 brine Substances 0.000 description 35
• 239000003054 catalyst Substances 0.000 description 35
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• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 35
• 229910052757 nitrogen Chemical group 0.000 description 33
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 31
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 31
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
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• 239000000908 ammonium hydroxide Substances 0.000 description 28
• 239000012043 crude product Substances 0.000 description 27
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 27
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
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• 239000000460 chlorine Substances 0.000 description 25
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• QDYBCIWLGJMJGO-UHFFFAOYSA-N dinitromethanone Chemical compound [O-][N+](=O)C(=O)[N+]([O-])=O QDYBCIWLGJMJGO-UHFFFAOYSA-N 0.000 description 21
• 238000005160 1H NMR spectroscopy Methods 0.000 description 20
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• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 15
• 239000002253 acid Substances 0.000 description 15
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• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
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• KNXQDJCZSVHEIW-UHFFFAOYSA-N (3-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(F)=C1 KNXQDJCZSVHEIW-UHFFFAOYSA-N 0.000 description 12
• IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 12
• 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 12
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 12
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• 239000000706 filtrate Substances 0.000 description 12
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