JP2006528147A - ヒスタミンｈ３受容体リガンドとしての置換ピペリジン - Google Patents

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Publication number

JP2006528147A

JP2006528147A JP2006520762A JP2006520762A JP2006528147A JP 2006528147 A JP2006528147 A JP 2006528147A JP 2006520762 A JP2006520762 A JP 2006520762A JP 2006520762 A JP2006520762 A JP 2006520762A JP 2006528147 A JP2006528147 A JP 2006528147A

Authority

JP

Japan

Prior art keywords

piperidinyl

alkyl

formula

compound

group

Prior art date

2003-07-18

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.)

Pending

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• 102000004384 Histamine H3 receptors Human genes 0.000 title description 7
• 108090000981 Histamine H3 receptors Proteins 0.000 title description 7
• 239000003446 ligand Substances 0.000 title description 2
• 150000003053 piperidines Chemical class 0.000 title description 2
• -1 piperidine ether derivatives Chemical class 0.000 claims abstract description 55
• 238000000034 method Methods 0.000 claims abstract description 54
• 238000002360 preparation method Methods 0.000 claims abstract description 12
• 208000012902 Nervous system disease Diseases 0.000 claims abstract description 6
• 208000025966 Neurological disease Diseases 0.000 claims abstract description 6
• 150000001875 compounds Chemical class 0.000 claims description 217
• 150000002500 ions Chemical class 0.000 claims description 74
• 125000000217 alkyl group Chemical group 0.000 claims description 59
• 150000003839 salts Chemical class 0.000 claims description 24
• 125000003118 aryl group Chemical group 0.000 claims description 23
• 125000005843 halogen group Chemical group 0.000 claims description 22
• 125000003545 alkoxy group Chemical group 0.000 claims description 21
• 229910052736 halogen Inorganic materials 0.000 claims description 13
• 150000002367 halogens Chemical class 0.000 claims description 12
• 125000000623 heterocyclic group Chemical group 0.000 claims description 12
• 125000001072 heteroaryl group Chemical group 0.000 claims description 11
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
• 229910005965 SO 2 Inorganic materials 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
• 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 7
• 125000001424 substituent group Chemical group 0.000 claims description 6
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 5
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 4
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 4
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 4
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
• ROFRIKRDIUUGLL-UHFFFAOYSA-N 3-methyl-5-[4-[4-(1-propan-2-ylpiperidin-4-yl)oxypiperidin-1-yl]phenyl]-1,2,4-oxadiazole Chemical compound C1CN(C(C)C)CCC1OC1CCN(C=2C=CC(=CC=2)C=2ON=C(C)N=2)CC1 ROFRIKRDIUUGLL-UHFFFAOYSA-N 0.000 claims description 4
• HCSPMMJLAZYFCT-UHFFFAOYSA-N 5-[4-(1-cyclobutylpiperidin-4-yl)oxypiperidin-1-yl]-2-(trifluoromethyl)pyrimidine Chemical compound C1=NC(C(F)(F)F)=NC=C1N1CCC(OC2CCN(CC2)C2CCC2)CC1 HCSPMMJLAZYFCT-UHFFFAOYSA-N 0.000 claims description 4
• 125000005947 C1-C6 alkylsulfonyloxy group Chemical group 0.000 claims description 4
• 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 4
• 125000003435 aroyl group Chemical group 0.000 claims description 4
• 125000005533 aryl carboxamido group Chemical group 0.000 claims description 4
• 125000005421 aryl sulfonamido group Chemical group 0.000 claims description 4
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
• 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 4
• 125000004104 aryloxy group Chemical group 0.000 claims description 4
• 239000004106 carminic acid Substances 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 229910052739 hydrogen Inorganic materials 0.000 claims description 4
• 239000001257 hydrogen Substances 0.000 claims description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 125000004043 oxo group Chemical group O=* 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• NRYGWLNOBIXJSR-UHFFFAOYSA-N 1-[4-[4-(1-cyclobutylpiperidin-4-yl)oxypiperidin-1-yl]phenyl]ethanone Chemical compound C1=CC(C(=O)C)=CC=C1N1CCC(OC2CCN(CC2)C2CCC2)CC1 NRYGWLNOBIXJSR-UHFFFAOYSA-N 0.000 claims description 3
• OBYBVWBWVBQDEC-UHFFFAOYSA-N 5-[4-(1-cyclobutylpiperidin-4-yl)oxypiperidin-1-yl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC=C1N1CCC(OC2CCN(CC2)C2CCC2)CC1 OBYBVWBWVBQDEC-UHFFFAOYSA-N 0.000 claims description 3
• 125000001589 carboacyl group Chemical group 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 3
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
• QLZASUPJZXESTL-UHFFFAOYSA-N 3-[4-(1-cyclobutylpiperidin-4-yl)oxypiperidin-1-yl]-6-(trifluoromethyl)pyridazine Chemical compound N1=NC(C(F)(F)F)=CC=C1N1CCC(OC2CCN(CC2)C2CCC2)CC1 QLZASUPJZXESTL-UHFFFAOYSA-N 0.000 claims description 2
• FZAXBPZVVJOFKX-UHFFFAOYSA-N 3-methyl-1,2,4-oxadiazole Chemical compound CC=1N=CON=1 FZAXBPZVVJOFKX-UHFFFAOYSA-N 0.000 claims description 2
• 125000003342 alkenyl group Chemical group 0.000 claims description 2
• 125000000304 alkynyl group Chemical group 0.000 claims description 2
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 2
• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims 2
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 64
• NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 abstract description 8
• 208000020016 psychiatric disease Diseases 0.000 abstract description 3
• 230000000926 neurological effect Effects 0.000 abstract description 2
• 230000000144 pharmacologic effect Effects 0.000 abstract description 2
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 426
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 256
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 125
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 110
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 96
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 91
• 238000006243 chemical reaction Methods 0.000 description 73
• 239000007787 solid Substances 0.000 description 72
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 71
• 239000000243 solution Substances 0.000 description 71
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 70
• YZTXFXXGWSOOIE-UHFFFAOYSA-N 1-cyclobutyl-4-piperidin-4-yloxypiperidine Chemical compound C1CCC1N1CCC(OC2CCNCC2)CC1 YZTXFXXGWSOOIE-UHFFFAOYSA-N 0.000 description 67
• 235000019439 ethyl acetate Nutrition 0.000 description 53
• 239000002904 solvent Substances 0.000 description 52
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 51
• 239000000741 silica gel Substances 0.000 description 50
• 229910002027 silica gel Inorganic materials 0.000 description 50
• 239000011541 reaction mixture Substances 0.000 description 49
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 48
• 239000012458 free base Substances 0.000 description 48
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 47
• 239000000047 product Substances 0.000 description 46
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 38
• 229910000027 potassium carbonate Inorganic materials 0.000 description 33
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
• 238000004587 chromatography analysis Methods 0.000 description 31
• 238000012799 strong cation exchange Methods 0.000 description 31
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 26
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
• 229910052763 palladium Inorganic materials 0.000 description 24
• JPGVTCZHQVDLFZ-UHFFFAOYSA-N 4-piperidin-4-yloxy-1-propan-2-ylpiperidine Chemical compound C1CN(C(C)C)CCC1OC1CCNCC1 JPGVTCZHQVDLFZ-UHFFFAOYSA-N 0.000 description 23
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 23
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
• 239000003921 oil Substances 0.000 description 22
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
• 239000012267 brine Substances 0.000 description 21
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
• 230000002829 reductive effect Effects 0.000 description 20
• 238000001704 evaporation Methods 0.000 description 19
• 210000004027 cell Anatomy 0.000 description 18
• 230000008020 evaporation Effects 0.000 description 18
• 239000012300 argon atmosphere Substances 0.000 description 17
• 239000003054 catalyst Substances 0.000 description 17
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 17
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 16
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 16
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 238000003756 stirring Methods 0.000 description 15
• 238000005984 hydrogenation reaction Methods 0.000 description 14
• 239000012044 organic layer Substances 0.000 description 14
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 13
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 13
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 12
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 12
• 235000011114 ammonium hydroxide Nutrition 0.000 description 12
• 230000009467 reduction Effects 0.000 description 12
• 238000006722 reduction reaction Methods 0.000 description 12
• 239000011734 sodium Substances 0.000 description 12
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
• 239000000284 extract Substances 0.000 description 10
• MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 10
• 230000003595 spectral effect Effects 0.000 description 10
• ZEMZPXWZVTUONV-UHFFFAOYSA-N 2-(2-dicyclohexylphosphanylphenyl)-n,n-dimethylaniline Chemical group CN(C)C1=CC=CC=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 ZEMZPXWZVTUONV-UHFFFAOYSA-N 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• 238000010992 reflux Methods 0.000 description 9
• 229920005989 resin Polymers 0.000 description 9
• 239000011347 resin Substances 0.000 description 9
• KMYDFNDFCUPNSQ-LBPRGKRZSA-N 1-[(2s)-butan-2-yl]-4-piperidin-4-yloxypiperidine Chemical compound C1CN([C@@H](C)CC)CCC1OC1CCNCC1 KMYDFNDFCUPNSQ-LBPRGKRZSA-N 0.000 description 8
• VPDIHEIVLHHEPA-UHFFFAOYSA-N 4-piperidin-4-yloxy-1-propan-2-ylpiperidine;dihydrochloride Chemical compound Cl.Cl.C1CN(C(C)C)CCC1OC1CCNCC1 VPDIHEIVLHHEPA-UHFFFAOYSA-N 0.000 description 8
• USHCECDZCXYARM-UHFFFAOYSA-N 5-[4-(1-cyclobutylpiperidin-4-yl)oxypiperidin-1-yl]pyrazine-2-carbonyl chloride;hydrochloride Chemical compound Cl.C1=NC(C(=O)Cl)=CN=C1N1CCC(OC2CCN(CC2)C2CCC2)CC1 USHCECDZCXYARM-UHFFFAOYSA-N 0.000 description 8
• MNNQIBXLAHVDDL-UHFFFAOYSA-N 5-bromopyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Br)C=N1 MNNQIBXLAHVDDL-UHFFFAOYSA-N 0.000 description 8
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
• 239000012131 assay buffer Substances 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• 229960001340 histamine Drugs 0.000 description 8
• 239000002609 medium Substances 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• 239000012279 sodium borohydride Substances 0.000 description 8
• 229910000033 sodium borohydride Inorganic materials 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• WDNUUFNTOFLJRA-UHFFFAOYSA-M tert-butyl 4-(1-benzylpyridin-1-ium-4-yl)oxypiperidine-1-carboxylate;bromide Chemical compound [Br-].C1CN(C(=O)OC(C)(C)C)CCC1OC(C=C1)=CC=[N+]1CC1=CC=CC=C1 WDNUUFNTOFLJRA-UHFFFAOYSA-M 0.000 description 8
• ALPNOHOFARYXFG-UHFFFAOYSA-N tert-butyl 4-pyridin-4-yloxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OC1=CC=NC=C1 ALPNOHOFARYXFG-UHFFFAOYSA-N 0.000 description 8
• JZCGFUPRXOWOIM-UHFFFAOYSA-N tert-butyl 5-[4-(1-cyclobutylpiperidin-4-yl)oxypiperidin-1-yl]pyridine-2-carboxylate Chemical compound C1=NC(C(=O)OC(C)(C)C)=CC=C1N1CCC(OC2CCN(CC2)C2CCC2)CC1 JZCGFUPRXOWOIM-UHFFFAOYSA-N 0.000 description 8
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 7
• HSVLDONTNWZJBX-UHFFFAOYSA-N 5-(4-bromo-2-fluorophenyl)-3-methyl-1,2,4-oxadiazole Chemical compound CC1=NOC(C=2C(=CC(Br)=CC=2)F)=N1 HSVLDONTNWZJBX-UHFFFAOYSA-N 0.000 description 7
• BPFHANHGLVWQMM-UHFFFAOYSA-N 5-bromo-n,n-diethylpyridine-2-carboxamide Chemical compound CCN(CC)C(=O)C1=CC=C(Br)C=N1 BPFHANHGLVWQMM-UHFFFAOYSA-N 0.000 description 7
• ZHCFLPPPBCZADJ-UHFFFAOYSA-N 6-[4-(1-cyclobutylpiperidin-4-yl)oxypiperidin-1-yl]pyridine-3-carboxylic acid;hydrochloride Chemical compound Cl.N1=CC(C(=O)O)=CC=C1N1CCC(OC2CCN(CC2)C2CCC2)CC1 ZHCFLPPPBCZADJ-UHFFFAOYSA-N 0.000 description 7
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 7
• 239000012448 Lithium borohydride Substances 0.000 description 7
• 150000001412 amines Chemical class 0.000 description 7
• 229910021529 ammonia Inorganic materials 0.000 description 7
• IKOBNRGCSHDXFP-UHFFFAOYSA-N azetidin-1-yl-(5-bromopyridin-2-yl)methanone Chemical compound N1=CC(Br)=CC=C1C(=O)N1CCC1 IKOBNRGCSHDXFP-UHFFFAOYSA-N 0.000 description 7
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
• 229910052794 bromium Inorganic materials 0.000 description 7
• 239000012043 crude product Substances 0.000 description 7
• 208000035475 disorder Diseases 0.000 description 7
• 229910052731 fluorine Inorganic materials 0.000 description 7
• 239000011737 fluorine Substances 0.000 description 7
• 239000012528 membrane Substances 0.000 description 7
• 239000012074 organic phase Substances 0.000 description 7
• 239000000843 powder Substances 0.000 description 7
• 229920006395 saturated elastomer Polymers 0.000 description 7
• 239000000377 silicon dioxide Substances 0.000 description 7
• 239000003981 vehicle Substances 0.000 description 7
• AIEGIFIEQXZBCP-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)pyrazine Chemical compound FC(F)(F)C1=CN=C(Cl)C=N1 AIEGIFIEQXZBCP-UHFFFAOYSA-N 0.000 description 6
• GIFDWXWNFKZVEI-UHFFFAOYSA-N 5-bromo-2-(trifluoromethyl)pyrimidine Chemical compound FC(F)(F)C1=NC=C(Br)C=N1 GIFDWXWNFKZVEI-UHFFFAOYSA-N 0.000 description 6
• WWTUTYGXBBXUPH-UHFFFAOYSA-N 6-[4-(1-propan-2-ylpiperidin-4-yl)oxypiperidin-1-yl]pyridine-3-carboxylic acid;hydrochloride Chemical compound Cl.C1CN(C(C)C)CCC1OC1CCN(C=2N=CC(=CC=2)C(O)=O)CC1 WWTUTYGXBBXUPH-UHFFFAOYSA-N 0.000 description 6
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 6
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
• 229960000583 acetic acid Drugs 0.000 description 6
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