CA2557801C - Glucopyranosyl-substituted benzol derivatives, drugs containing said compounds, the use thereof and method for the production thereof - Google Patents

Info

Publication number

CA2557801C

CA2557801C CA2557801A CA2557801A CA2557801C CA 2557801 C CA2557801 C CA 2557801C CA 2557801 A CA2557801 A CA 2557801A CA 2557801 A CA2557801 A CA 2557801A CA 2557801 C CA2557801 C CA 2557801C

Authority

CA

Canada

Prior art keywords

benzene

glucopyranos

benzyl

yloxy

group

Prior art date

2004-03-16

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.)

Expired - Lifetime

Links

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• Global Dossier
• CIPO
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• 150000001875 compounds Chemical class 0.000 title claims abstract description 125
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical class C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 title claims description 106
• 239000003814 drug Chemical class 0.000 title claims description 8
• 238000000034 method Methods 0.000 title description 23
• 238000004519 manufacturing process Methods 0.000 title description 6
• 229940079593 drug Drugs 0.000 title description 3
• 150000003839 salts Chemical class 0.000 claims abstract description 41
• 102100037202 Sodium/myo-inositol cotransporter 2 Human genes 0.000 claims abstract description 17
• 101710090560 Sodium/myo-inositol cotransporter 2 Proteins 0.000 claims abstract description 17
• 108091006269 SLC5A2 Proteins 0.000 claims abstract description 16
• 102100020888 Sodium/glucose cotransporter 2 Human genes 0.000 claims abstract description 16
• 230000005764 inhibitory process Effects 0.000 claims abstract description 9
• -1 cyano, methyl Chemical group 0.000 claims description 224
• 229910052739 hydrogen Inorganic materials 0.000 claims description 73
• 239000001257 hydrogen Substances 0.000 claims description 73
• 239000000460 chlorine Chemical group 0.000 claims description 69
• 229910052731 fluorine Inorganic materials 0.000 claims description 56
• 239000011737 fluorine Chemical group 0.000 claims description 54
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 43
• 229910052801 chlorine Inorganic materials 0.000 claims description 39
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 38
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 34
• 229910052794 bromium Inorganic materials 0.000 claims description 28
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 24
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 24
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 22
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Chemical group C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 20
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
• 125000000217 alkyl group Chemical group 0.000 claims description 15
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
• 238000002360 preparation method Methods 0.000 claims description 13
• 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 12
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
• 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 claims description 3
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 3
• 229960003105 metformin Drugs 0.000 claims description 3
• 150000007522 mineralic acids Chemical class 0.000 claims description 3
• 150000007524 organic acids Chemical class 0.000 claims description 3
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
• 239000002552 dosage form Substances 0.000 claims description 2
• 150000002431 hydrogen Chemical group 0.000 claims 3
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
• 239000000203 mixture Substances 0.000 abstract description 56
• 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 19
• 208000030159 metabolic disease Diseases 0.000 abstract description 6
• 239000000243 solution Substances 0.000 description 138
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 114
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 71
• 238000001819 mass spectrum Methods 0.000 description 53
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 50
• 235000002639 sodium chloride Nutrition 0.000 description 43
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
• 238000006243 chemical reaction Methods 0.000 description 41
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
• 239000002904 solvent Substances 0.000 description 38
• 125000001153 fluoro group Chemical group F* 0.000 description 34
• 239000013543 active substance Substances 0.000 description 33
• 125000003118 aryl group Chemical group 0.000 description 33
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
• 239000012074 organic phase Substances 0.000 description 28
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 27
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
• 229910052938 sodium sulfate Inorganic materials 0.000 description 25
• 235000011152 sodium sulphate Nutrition 0.000 description 25
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 24
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 23
• 239000000741 silica gel Substances 0.000 description 23
• 229910002027 silica gel Inorganic materials 0.000 description 23
• 125000001424 substituent group Chemical group 0.000 description 21
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 20
• RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 20
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
• 125000000392 cycloalkenyl group Chemical group 0.000 description 20
• 125000000753 cycloalkyl group Chemical group 0.000 description 20
• 238000003786 synthesis reaction Methods 0.000 description 20
• 235000011167 hydrochloric acid Nutrition 0.000 description 19
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 125000000304 alkynyl group Chemical group 0.000 description 18
• 230000015572 biosynthetic process Effects 0.000 description 18
• 125000004093 cyano group Chemical group *C#N 0.000 description 18
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 17
• 125000003342 alkenyl group Chemical group 0.000 description 17
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 17
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 17
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 16
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 15
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
• 239000002253 acid Substances 0.000 description 15
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
• 210000004027 cell Anatomy 0.000 description 14
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 13
• 229910052751 metal Inorganic materials 0.000 description 13
• 239000002184 metal Substances 0.000 description 13
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
• 229910052786 argon Inorganic materials 0.000 description 12
• 239000003054 catalyst Substances 0.000 description 12
• 229960004132 diethyl ether Drugs 0.000 description 12
• 229910052736 halogen Inorganic materials 0.000 description 12
• 125000001072 heteroaryl group Chemical group 0.000 description 12
• 239000008194 pharmaceutical composition Substances 0.000 description 12
• 235000017557 sodium bicarbonate Nutrition 0.000 description 12
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 11
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 11
• 125000006239 protecting group Chemical group 0.000 description 11
• 229910052717 sulfur Inorganic materials 0.000 description 11
• 102000000070 Sodium-Glucose Transport Proteins Human genes 0.000 description 10
• 108010080361 Sodium-Glucose Transport Proteins Proteins 0.000 description 10
• 229910002091 carbon monoxide Inorganic materials 0.000 description 10
• 230000000875 corresponding effect Effects 0.000 description 10
• 238000010586 diagram Methods 0.000 description 10
• 239000003112 inhibitor Substances 0.000 description 10
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
• 230000002265 prevention Effects 0.000 description 10
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
• 239000003826 tablet Substances 0.000 description 10
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• 229960000583 acetic acid Drugs 0.000 description 9
• 125000005129 aryl carbonyl group Chemical group 0.000 description 9
• 150000002367 halogens Chemical group 0.000 description 9
• 230000002401 inhibitory effect Effects 0.000 description 9
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 9
• 235000011054 acetic acid Nutrition 0.000 description 8
• 239000005557 antagonist Substances 0.000 description 8
• 239000002775 capsule Substances 0.000 description 8
• 125000004432 carbon atom Chemical group C* 0.000 description 8
• 229910052740 iodine Inorganic materials 0.000 description 8
• 150000002902 organometallic compounds Chemical class 0.000 description 8
• 239000011780 sodium chloride Substances 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 7
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 7
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 7
• 201000010099 disease Diseases 0.000 description 7
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 7
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 7
• 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 7
• OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 7
• 230000008569 process Effects 0.000 description 7
• 239000000047 product Substances 0.000 description 7
• 238000003756 stirring Methods 0.000 description 7
• 229910052723 transition metal Inorganic materials 0.000 description 7
• 150000003624 transition metals Chemical class 0.000 description 7
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 7
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
• PHOQVHQSTUBQQK-SQOUGZDYSA-N D-glucono-1,5-lactone Chemical compound OC[C@H]1OC(=O)[C@H](O)[C@@H](O)[C@@H]1O PHOQVHQSTUBQQK-SQOUGZDYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
• 239000002841 Lewis acid Substances 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
• 239000008346 aqueous phase Substances 0.000 description 6
• 125000004391 aryl sulfonyl group Chemical group 0.000 description 6
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
• 239000003638 chemical reducing agent Substances 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 238000005859 coupling reaction Methods 0.000 description 6
• 206010012601 diabetes mellitus Diseases 0.000 description 6
• CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical compound C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 0.000 description 6
• 239000008101 lactose Substances 0.000 description 6
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 6
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 125000004076 pyridyl group Chemical group 0.000 description 6
• 239000001117 sulphuric acid Substances 0.000 description 6
• 235000011149 sulphuric acid Nutrition 0.000 description 6
• CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 6
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
• 229910015900 BF3 Inorganic materials 0.000 description 5
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
• 125000004036 acetal group Chemical group 0.000 description 5
• 239000000556 agonist Substances 0.000 description 5
• 125000004104 aryloxy group Chemical group 0.000 description 5
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 5
• YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 5
• 239000003085 diluting agent Substances 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 5
• 235000012209 glucono delta-lactone Nutrition 0.000 description 5
• 229960003681 gluconolactone Drugs 0.000 description 5
• 239000013067 intermediate product Substances 0.000 description 5
• 150000002576 ketones Chemical class 0.000 description 5
• 235000019359 magnesium stearate Nutrition 0.000 description 5
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 5
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
• CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 5
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 4
• 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 4
• 229920002261 Corn starch Polymers 0.000 description 4
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• 125000005100 aryl amino carbonyl group Chemical group 0.000 description 4
• 125000004658 aryl carbonyl amino group Chemical group 0.000 description 4
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• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 4
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 4
• 229910052799 carbon Inorganic materials 0.000 description 4
• 239000000969 carrier Substances 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 4
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• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
• 125000002541 furyl group Chemical group 0.000 description 4
• 125000005222 heteroarylaminocarbonyl group Chemical group 0.000 description 4
• 125000005223 heteroarylcarbonyl group Chemical group 0.000 description 4
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• 125000001041 indolyl group Chemical group 0.000 description 4
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 4
• 150000007517 lewis acids Chemical class 0.000 description 4
• 229910052744 lithium Inorganic materials 0.000 description 4
• UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 4
• 239000011777 magnesium Substances 0.000 description 4
• 229910052749 magnesium Inorganic materials 0.000 description 4
• 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 4
• 125000001624 naphthyl group Chemical group 0.000 description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 description 4
• 125000004430 oxygen atom Chemical group O* 0.000 description 4
• 229910052763 palladium Inorganic materials 0.000 description 4
• 150000003214 pyranose derivatives Chemical group 0.000 description 4
• 125000000168 pyrrolyl group Chemical group 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 238000006722 reduction reaction Methods 0.000 description 4
• 239000012279 sodium borohydride Substances 0.000 description 4
• 229910000033 sodium borohydride Inorganic materials 0.000 description 4
• 239000000829 suppository Substances 0.000 description 4
• 125000001544 thienyl group Chemical group 0.000 description 4
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 4
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