NO330118B1 - Nye forbindelser, farmasoytisk sammensetning, anvendelse - Google Patents

Info

Publication number

NO330118B1

NO330118B1 NO20045659A NO20045659A NO330118B1 NO 330118 B1 NO330118 B1 NO 330118B1 NO 20045659 A NO20045659 A NO 20045659A NO 20045659 A NO20045659 A NO 20045659A NO 330118 B1 NO330118 B1 NO 330118B1

Authority

NO

Norway

Prior art keywords

tetrahydro

methoxy

benzazepine

alkyl

methyl

Prior art date

2002-05-29

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 217
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 8
• -1 hydroxyC1-6alkyl Chemical group 0.000 claims abstract description 53
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 46
• 239000001257 hydrogen Substances 0.000 claims abstract description 45
• 150000003839 salts Chemical class 0.000 claims abstract description 39
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 32
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 31
• 150000002431 hydrogen Chemical group 0.000 claims abstract description 27
• 239000012453 solvate Substances 0.000 claims abstract description 24
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 23
• 150000002367 halogens Chemical group 0.000 claims abstract description 23
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 22
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 19
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 18
• 238000011282 treatment Methods 0.000 claims abstract description 17
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 17
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 16
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 15
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 12
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 12
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 10
• 239000001301 oxygen Substances 0.000 claims abstract description 10
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 10
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 8
• 125000004429 atom Chemical group 0.000 claims abstract description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
• 125000001424 substituent group Chemical group 0.000 claims description 21
• 125000003118 aryl group Chemical group 0.000 claims description 19
• 125000000623 heterocyclic group Chemical group 0.000 claims description 13
• 229920006395 saturated elastomer Polymers 0.000 claims description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
• 208000035475 disorder Diseases 0.000 claims description 7
• 208000028017 Psychotic disease Diseases 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 6
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 5
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 5
• 208000019901 Anxiety disease Diseases 0.000 claims description 5
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
• 230000036506 anxiety Effects 0.000 claims description 5
• 125000005842 heteroatom Chemical group 0.000 claims description 5
• 125000002950 monocyclic group Chemical group 0.000 claims description 5
• 201000000980 schizophrenia Diseases 0.000 claims description 5
• 208000018737 Parkinson disease Diseases 0.000 claims description 4
• 208000010877 cognitive disease Diseases 0.000 claims description 4
• 125000001624 naphthyl group Chemical group 0.000 claims description 4
• 238000002360 preparation method Methods 0.000 claims description 4
• 201000009032 substance abuse Diseases 0.000 claims description 4
• 231100000736 substance abuse Toxicity 0.000 claims description 4
• 208000011117 substance-related disease Diseases 0.000 claims description 4
• 229910052717 sulfur Inorganic materials 0.000 claims description 4
• 239000011593 sulfur Substances 0.000 claims description 4
• COCPXRGCLUOMPQ-UHFFFAOYSA-N 4-[(8-methoxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)sulfonyl]-n-[(2-methoxyphenyl)methyl]aniline Chemical compound COC1=CC=CC=C1CNC1=CC=C(S(=O)(=O)C=2C(=CC=3CCN(C)CCC=3C=2)OC)C=C1 COCPXRGCLUOMPQ-UHFFFAOYSA-N 0.000 claims description 3
• KJDKDTRDWXCQBE-UHFFFAOYSA-N 6-ethoxy-7-[4-[(4-fluorophenyl)methoxy]phenyl]sulfonyl-1,2,3,4-tetrahydroisoquinoline;hydrochloride Chemical compound Cl.CCOC1=CC=2CCNCC=2C=C1S(=O)(=O)C(C=C1)=CC=C1OCC1=CC=C(F)C=C1 KJDKDTRDWXCQBE-UHFFFAOYSA-N 0.000 claims description 3
• SVXRQILAKMZNDQ-UHFFFAOYSA-N 7-[4-[(4-chlorophenoxy)methyl]phenyl]sulfonyl-8-ethoxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound CCOC1=CC=2CCN(C)CCC=2C=C1S(=O)(=O)C(C=C1)=CC=C1COC1=CC=C(Cl)C=C1 SVXRQILAKMZNDQ-UHFFFAOYSA-N 0.000 claims description 3
• SEKXUECQSDMHON-UHFFFAOYSA-N 7-[4-[(4-fluorophenoxy)methyl]phenyl]sulfonyl-n,n,3-trimethyl-1,2,4,5-tetrahydro-3-benzazepin-8-amine Chemical compound CN(C)C1=CC=2CCN(C)CCC=2C=C1S(=O)(=O)C(C=C1)=CC=C1COC1=CC=C(F)C=C1 SEKXUECQSDMHON-UHFFFAOYSA-N 0.000 claims description 3
• 208000028698 Cognitive impairment Diseases 0.000 claims description 3
• 108050004812 Dopamine receptor Proteins 0.000 claims description 3
• 102000015554 Dopamine receptor Human genes 0.000 claims description 3
• 125000003282 alkyl amino group Chemical group 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 230000000142 dyskinetic effect Effects 0.000 claims description 3
• JBVJZWOTVDROBX-UHFFFAOYSA-N n-[[4-[(8-ethoxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)sulfonyl]phenyl]methyl]-2-methoxyaniline Chemical compound CCOC1=CC=2CCN(C)CCC=2C=C1S(=O)(=O)C(C=C1)=CC=C1CNC1=CC=CC=C1OC JBVJZWOTVDROBX-UHFFFAOYSA-N 0.000 claims description 3
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
• 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 2
• YRIMOYWLZQPOEE-UHFFFAOYSA-N 4-[(8-methoxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)sulfonyl]-n-phenylaniline Chemical compound COC1=CC=2CCN(C)CCC=2C=C1S(=O)(=O)C(C=C1)=CC=C1NC1=CC=CC=C1 YRIMOYWLZQPOEE-UHFFFAOYSA-N 0.000 claims description 2
• TWLOBNIIGJZSCO-UHFFFAOYSA-N 5-methoxy-2-methyl-6-[4-[[3-(trifluoromethyl)phenyl]methoxy]phenyl]sulfonyl-1,3-dihydroisoindole Chemical compound COC1=CC=2CN(C)CC=2C=C1S(=O)(=O)C(C=C1)=CC=C1OCC1=CC=CC(C(F)(F)F)=C1 TWLOBNIIGJZSCO-UHFFFAOYSA-N 0.000 claims description 2
• GBFLXYISFPKKBT-UHFFFAOYSA-N 7-(3-phenylmethoxyphenyl)sulfonyl-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C=1C=C2CCNCCC2=CC=1S(=O)(=O)C(C=1)=CC=CC=1OCC1=CC=CC=C1 GBFLXYISFPKKBT-UHFFFAOYSA-N 0.000 claims description 2
• BRSYMTIKEANUDA-UHFFFAOYSA-N 7-[4-[(3-fluorophenyl)methoxy]phenyl]sulfonyl-6-methoxy-1,2,3,4-tetrahydroisoquinoline Chemical compound COC1=CC=2CCNCC=2C=C1S(=O)(=O)C(C=C1)=CC=C1OCC1=CC=CC(F)=C1 BRSYMTIKEANUDA-UHFFFAOYSA-N 0.000 claims description 2
• GHQFJSFJVANWBE-UHFFFAOYSA-N 7-[4-[(4-chlorophenoxy)methyl]phenyl]sulfonyl-6-methoxy-1,2,3,4-tetrahydroisoquinoline;hydrochloride Chemical compound Cl.COC1=CC=2CCNCC=2C=C1S(=O)(=O)C(C=C1)=CC=C1COC1=CC=C(Cl)C=C1 GHQFJSFJVANWBE-UHFFFAOYSA-N 0.000 claims description 2
• HIBWHHQXUSKNOV-UHFFFAOYSA-N 7-[4-[(4-chlorophenyl)methoxy]phenyl]sulfonyl-8-methoxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound COC1=CC=2CCN(C)CCC=2C=C1S(=O)(=O)C(C=C1)=CC=C1OCC1=CC=C(Cl)C=C1 HIBWHHQXUSKNOV-UHFFFAOYSA-N 0.000 claims description 2
• QXSWMHVVVHYBMA-UHFFFAOYSA-N 7-[4-[(4-fluorophenyl)methyl]phenyl]sulfonyl-8-methoxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound COC1=CC=2CCN(C)CCC=2C=C1S(=O)(=O)C(C=C1)=CC=C1CC1=CC=C(F)C=C1 QXSWMHVVVHYBMA-UHFFFAOYSA-N 0.000 claims description 2
• ZYFKSYKCFFNTMF-UHFFFAOYSA-N 8-methoxy-3-methyl-7-(3-phenoxyphenyl)sulfonyl-1,2,4,5-tetrahydro-3-benzazepine Chemical compound COC1=CC=2CCN(C)CCC=2C=C1S(=O)(=O)C(C=1)=CC=CC=1OC1=CC=CC=C1 ZYFKSYKCFFNTMF-UHFFFAOYSA-N 0.000 claims description 2
• GJMUNWIPYJCMGG-UHFFFAOYSA-N 8-methoxy-7-(3-phenoxyphenyl)sulfonyl-2,3,4,5-tetrahydro-1h-3-benzazepine Chemical group COC1=CC=2CCNCCC=2C=C1S(=O)(=O)C(C=1)=CC=CC=1OC1=CC=CC=C1 GJMUNWIPYJCMGG-UHFFFAOYSA-N 0.000 claims description 2
• 208000020925 Bipolar disease Diseases 0.000 claims description 2
• 125000001589 carboacyl group Chemical group 0.000 claims description 2
• AKULVMIPWCHBEF-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-4-[(8-methoxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)sulfonyl]aniline Chemical compound COC1=CC=2CCN(C)CCC=2C=C1S(=O)(=O)C(C=C1)=CC=C1NCC1=CC=C(F)C=C1 AKULVMIPWCHBEF-UHFFFAOYSA-N 0.000 claims description 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
• 238000004519 manufacturing process Methods 0.000 claims 1
• AORPHQUMVNMHPO-UHFFFAOYSA-N n-[(3-methoxyphenyl)methyl]-4-[(6-methoxy-1,2,3,4-tetrahydroisoquinolin-7-yl)sulfonyl]-n-methylaniline Chemical compound COC1=CC=CC(CN(C)C=2C=CC(=CC=2)S(=O)(=O)C=2C(=CC=3CCNCC=3C=2)OC)=C1 AORPHQUMVNMHPO-UHFFFAOYSA-N 0.000 claims 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
• 125000000753 cycloalkyl group Chemical group 0.000 abstract description 7
• 125000003107 substituted aryl group Chemical group 0.000 abstract description 7
• 239000000164 antipsychotic agent Substances 0.000 abstract description 4
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 1
• 229940005529 antipsychotics Drugs 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 163
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 127
• 239000000203 mixture Substances 0.000 description 119
• 239000000243 solution Substances 0.000 description 106
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 105
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 91
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 76
• 238000000034 method Methods 0.000 description 64
• 238000005481 NMR spectroscopy Methods 0.000 description 63
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 59
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 50
• 235000019439 ethyl acetate Nutrition 0.000 description 45
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
• 239000007787 solid Substances 0.000 description 42
• 239000000047 product Substances 0.000 description 38
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 38
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 34
• 239000012044 organic layer Substances 0.000 description 32
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
• 238000004587 chromatography analysis Methods 0.000 description 29
• 239000000377 silicon dioxide Substances 0.000 description 28
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
• 239000012267 brine Substances 0.000 description 25
• 238000006243 chemical reaction Methods 0.000 description 25
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
• 239000002585 base Substances 0.000 description 23
• 239000003921 oil Substances 0.000 description 23
• 235000019198 oils Nutrition 0.000 description 23
• 239000002904 solvent Substances 0.000 description 22
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• 150000003840 hydrochlorides Chemical class 0.000 description 21
• 238000001816 cooling Methods 0.000 description 17
• 229910000104 sodium hydride Inorganic materials 0.000 description 17
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 16
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 16
• 239000000460 chlorine Substances 0.000 description 16
• 229910052731 fluorine Inorganic materials 0.000 description 16
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
• 239000012312 sodium hydride Substances 0.000 description 16
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 15
• 229910052801 chlorine Inorganic materials 0.000 description 15
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 14
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 14
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 14
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
• 239000000725 suspension Substances 0.000 description 14
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 13
• 239000011737 fluorine Substances 0.000 description 13
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 12
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
• 235000019341 magnesium sulphate Nutrition 0.000 description 12
• 238000000746 purification Methods 0.000 description 12
• 102000005962 receptors Human genes 0.000 description 12
• 108020003175 receptors Proteins 0.000 description 12
• 235000017557 sodium bicarbonate Nutrition 0.000 description 12
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 11
• 239000012442 inert solvent Substances 0.000 description 10
• 239000010410 layer Substances 0.000 description 10
• NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 10
• 230000009467 reduction Effects 0.000 description 10
• 238000006722 reduction reaction Methods 0.000 description 10
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 10
• NNLXSIBXDYFUBV-UHFFFAOYSA-N 3-(2,2,2-trifluoroacetyl)-1,2,4,5-tetrahydro-3-benzazepine-7-sulfonyl fluoride Chemical compound C1CN(C(=O)C(F)(F)F)CCC2=CC=C(S(F)(=O)=O)C=C21 NNLXSIBXDYFUBV-UHFFFAOYSA-N 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• 229910052794 bromium Inorganic materials 0.000 description 9
• 125000004432 carbon atom Chemical group C* 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 8
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
• 235000019253 formic acid Nutrition 0.000 description 8
• 229910052938 sodium sulfate Inorganic materials 0.000 description 8
• 235000011152 sodium sulphate Nutrition 0.000 description 8
• 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 description 7
• 230000010933 acylation Effects 0.000 description 7
• 238000005917 acylation reaction Methods 0.000 description 7
• 229910052786 argon Inorganic materials 0.000 description 7
• 230000027455 binding Effects 0.000 description 7
• UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 7
• 210000004027 cell Anatomy 0.000 description 7
• 239000013078 crystal Substances 0.000 description 7
• 239000012458 free base Substances 0.000 description 7
• 238000010438 heat treatment Methods 0.000 description 7
• 229910000027 potassium carbonate Inorganic materials 0.000 description 7
• 239000011541 reaction mixture Substances 0.000 description 7
• 238000006485 reductive methylation reaction Methods 0.000 description 7
• 238000010992 reflux Methods 0.000 description 7
• KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
• 238000005160 1H NMR spectroscopy Methods 0.000 description 6
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 6
• 238000001704 evaporation Methods 0.000 description 6
• 230000008020 evaporation Effects 0.000 description 6
• 239000000284 extract Substances 0.000 description 6
• 238000007429 general method Methods 0.000 description 6
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 6
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
• 239000011698 potassium fluoride Substances 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
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