CA2679310A1 - Tetrasubstituted glucopyranosylated benzene derivatives, medicaments containing such compounds, their use and process for their manufacture - Google Patents

Info

Publication number

CA2679310A1

CA2679310A1 CA002679310A CA2679310A CA2679310A1 CA 2679310 A1 CA2679310 A1 CA 2679310A1 CA 002679310 A CA002679310 A CA 002679310A CA 2679310 A CA2679310 A CA 2679310A CA 2679310 A1 CA2679310 A1 CA 2679310A1

Authority

CA

Canada

Prior art keywords

alkyl

groups

compound

group

aryl

Prior art date

2007-02-21

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.)

Withdrawn

Links

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• CIPO
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• 150000001875 compounds Chemical class 0.000 title claims abstract description 120
• 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title claims abstract description 31
• 238000004519 manufacturing process Methods 0.000 title claims description 8
• 238000000034 method Methods 0.000 title description 23
• 230000008569 process Effects 0.000 title description 9
• 239000003814 drug Substances 0.000 title description 4
• 239000000203 mixture Substances 0.000 claims abstract description 45
• 150000003839 salts Chemical class 0.000 claims abstract description 42
• 208000030159 metabolic disease Diseases 0.000 claims abstract description 8
• -1 C1-4-alkylcarbonyl Chemical group 0.000 claims description 104
• 229910052739 hydrogen Inorganic materials 0.000 claims description 49
• 239000001257 hydrogen Substances 0.000 claims description 46
• 238000006243 chemical reaction Methods 0.000 claims description 38
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 36
• 125000003118 aryl group Chemical group 0.000 claims description 31
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 30
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
• 239000000460 chlorine Substances 0.000 claims description 30
• 229910052801 chlorine Inorganic materials 0.000 claims description 30
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 29
• 229910052794 bromium Inorganic materials 0.000 claims description 23
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 22
• 229910052731 fluorine Inorganic materials 0.000 claims description 22
• 239000011737 fluorine Substances 0.000 claims description 21
• 239000008194 pharmaceutical composition Substances 0.000 claims description 21
• 125000001424 substituent group Chemical group 0.000 claims description 21
• 125000000217 alkyl group Chemical group 0.000 claims description 20
• 229910052751 metal Inorganic materials 0.000 claims description 19
• 239000002184 metal Substances 0.000 claims description 19
• 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 18
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 17
• 229910052736 halogen Inorganic materials 0.000 claims description 17
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 15
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 15
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
• 239000002253 acid Substances 0.000 claims description 14
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
• 150000002367 halogens Chemical group 0.000 claims description 13
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
• 125000006239 protecting group Chemical group 0.000 claims description 13
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 12
• 102000000070 Sodium-Glucose Transport Proteins Human genes 0.000 claims description 11
• 108010080361 Sodium-Glucose Transport Proteins Proteins 0.000 claims description 11
• 102100037202 Sodium/myo-inositol cotransporter 2 Human genes 0.000 claims description 11
• 101710090560 Sodium/myo-inositol cotransporter 2 Proteins 0.000 claims description 11
• 201000010099 disease Diseases 0.000 claims description 11
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
• 230000002401 inhibitory effect Effects 0.000 claims description 11
• 229910052740 iodine Inorganic materials 0.000 claims description 11
• 230000002265 prevention Effects 0.000 claims description 11
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
• 125000004036 acetal group Chemical group 0.000 claims description 10
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 10
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
• 125000006702 (C1-C18) alkyl group Chemical group 0.000 claims description 9
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 9
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 9
• 108091006269 SLC5A2 Proteins 0.000 claims description 8
• 125000004432 carbon atom Chemical group C* 0.000 claims description 8
• 206010012601 diabetes mellitus Diseases 0.000 claims description 8
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 7
• 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 claims description 7
• 239000002841 Lewis acid Substances 0.000 claims description 7
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
• 239000003638 chemical reducing agent Substances 0.000 claims description 7
• 229960003681 gluconolactone Drugs 0.000 claims description 7
• ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 7
• 125000001624 naphthyl group Chemical group 0.000 claims description 7
• 150000003214 pyranose derivatives Chemical group 0.000 claims description 7
• 210000002237 B-cell of pancreatic islet Anatomy 0.000 claims description 6
• 239000007848 Bronsted acid Substances 0.000 claims description 6
• 208000008589 Obesity Diseases 0.000 claims description 6
• 239000003085 diluting agent Substances 0.000 claims description 6
• 125000001153 fluoro group Chemical group F* 0.000 claims description 6
• 235000012209 glucono delta-lactone Nutrition 0.000 claims description 6
• 210000004185 liver Anatomy 0.000 claims description 6
• 235000020824 obesity Nutrition 0.000 claims description 6
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 5
• 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 5
• 230000002159 abnormal effect Effects 0.000 claims description 5
• 238000009825 accumulation Methods 0.000 claims description 5
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
• 239000000969 carrier Substances 0.000 claims description 5
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 5
• 150000002902 organometallic compounds Chemical class 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 5
• 239000005977 Ethylene Substances 0.000 claims description 4
• 206010020772 Hypertension Diseases 0.000 claims description 4
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 239000002934 diuretic Substances 0.000 claims description 4
• 125000001072 heteroaryl group Chemical group 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 238000006478 transmetalation reaction Methods 0.000 claims description 4
• 201000001320 Atherosclerosis Diseases 0.000 claims description 3
• 206010007558 Cardiac failure chronic Diseases 0.000 claims description 3
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
• 125000000304 alkynyl group Chemical group 0.000 claims description 3
• 239000003795 chemical substances by application Substances 0.000 claims description 3
• 230000007850 degeneration Effects 0.000 claims description 3
• 150000002012 dioxanes Chemical group 0.000 claims description 3
• 230000006806 disease prevention Effects 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
• 235000005985 organic acids Nutrition 0.000 claims description 3
• 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 3
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
• 208000010444 Acidosis Diseases 0.000 claims description 2
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
• 208000032928 Dyslipidaemia Diseases 0.000 claims description 2
• 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 2
• 201000001431 Hyperuricemia Diseases 0.000 claims description 2
• 208000013016 Hypoglycemia Diseases 0.000 claims description 2
• 206010022489 Insulin Resistance Diseases 0.000 claims description 2
• 208000007976 Ketosis Diseases 0.000 claims description 2
• 208000001145 Metabolic Syndrome Diseases 0.000 claims description 2
• 206010027417 Metabolic acidosis Diseases 0.000 claims description 2
• 206010030113 Oedema Diseases 0.000 claims description 2
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 2
• 150000003855 acyl compounds Chemical class 0.000 claims description 2
• 230000010933 acylation Effects 0.000 claims description 2
• 238000005917 acylation reaction Methods 0.000 claims description 2
• 125000003342 alkenyl group Chemical group 0.000 claims description 2
• 125000001118 alkylidene group Chemical group 0.000 claims description 2
• 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 2
• 125000005163 aryl sulfanyl group Chemical group 0.000 claims description 2
• 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 2
• 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 2
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
• 125000004104 aryloxy group Chemical group 0.000 claims description 2
• 230000001882 diuretic effect Effects 0.000 claims description 2
• 208000018914 glucose metabolism disease Diseases 0.000 claims description 2
• 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 2
• 125000005224 heteroarylcarbonylamino group Chemical group 0.000 claims description 2
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
• 125000005150 heteroarylsulfinyl group Chemical group 0.000 claims description 2
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 2
• 230000035879 hyperinsulinaemia Effects 0.000 claims description 2
• 239000011630 iodine Substances 0.000 claims description 2
• 230000004140 ketosis Effects 0.000 claims description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
• 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 claims description 2
• 229910052717 sulfur Inorganic materials 0.000 claims description 2
• 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims 5
• 150000002431 hydrogen Chemical class 0.000 claims 4
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 3
• 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 2
• 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims 2
• 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims 1
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 1
• 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims 1
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
• 102000058081 Sodium-Glucose Transporter 2 Human genes 0.000 claims 1
• 230000003276 anti-hypertensive effect Effects 0.000 claims 1
• 125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
• 239000000243 solution Substances 0.000 description 35
• 239000013543 active substance Substances 0.000 description 33
• 235000002639 sodium chloride Nutrition 0.000 description 33
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
• 239000002904 solvent Substances 0.000 description 25
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
• 238000003786 synthesis reaction Methods 0.000 description 17
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 15
• 230000015572 biosynthetic process Effects 0.000 description 15
• 238000001819 mass spectrum Methods 0.000 description 15
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
• 210000004027 cell Anatomy 0.000 description 14
• 229960000583 acetic acid Drugs 0.000 description 12
• 230000000875 corresponding effect Effects 0.000 description 12
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
• 238000002360 preparation method Methods 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 10
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 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
• 230000009467 reduction Effects 0.000 description 10
• 238000006722 reduction reaction Methods 0.000 description 10
• 239000003826 tablet Substances 0.000 description 10
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
• 229910052723 transition metal Inorganic materials 0.000 description 10
• 150000003624 transition metals Chemical class 0.000 description 10
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
• 239000012267 brine Substances 0.000 description 9
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 9
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 8
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
• 239000005557 antagonist Substances 0.000 description 8
• 239000002775 capsule Substances 0.000 description 8
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 7
• 102100020888 Sodium/glucose cotransporter 2 Human genes 0.000 description 7
• 239000003054 catalyst Substances 0.000 description 7
• 229910052744 lithium Inorganic materials 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
• 229910052938 sodium sulfate Inorganic materials 0.000 description 7
• 235000011152 sodium sulphate Nutrition 0.000 description 7
• 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
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 6
• 229910052799 carbon Inorganic materials 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
• 229960004132 diethyl ether Drugs 0.000 description 6
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 6
• 239000008101 lactose Substances 0.000 description 6
• 239000011777 magnesium Substances 0.000 description 6
• 229910052749 magnesium Inorganic materials 0.000 description 6
• 239000012044 organic layer Substances 0.000 description 6
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 6
• CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 6
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
• 229920002261 Corn starch Polymers 0.000 description 5
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
• 239000000556 agonist Substances 0.000 description 5
• 238000004587 chromatography analysis Methods 0.000 description 5
• 239000008120 corn starch Substances 0.000 description 5
• CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical compound C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 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
• PSCMQHVBLHHWTO-UHFFFAOYSA-K indium(iii) chloride Chemical compound Cl[In](Cl)Cl PSCMQHVBLHHWTO-UHFFFAOYSA-K 0.000 description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
• 235000019359 magnesium stearate Nutrition 0.000 description 5
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
• 239000012074 organic phase Substances 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
• 239000002243 precursor Substances 0.000 description 5
• 239000000741 silica gel Substances 0.000 description 5
• 229910002027 silica gel Inorganic materials 0.000 description 5
• 235000017557 sodium bicarbonate Nutrition 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
• 239000007787 solid Substances 0.000 description 5
• 239000007858 starting material Substances 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 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
• 208000004930 Fatty Liver Diseases 0.000 description 4
• 206010019708 Hepatic steatosis Diseases 0.000 description 4
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
• 150000007513 acids Chemical class 0.000 description 4
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 4
• 229910052796 boron Inorganic materials 0.000 description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• 239000012043 crude product Substances 0.000 description 4
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