AU2002338896B2 - Quinoline derivatives as ligands for the neuropeptide Y receptor - Google Patents

Info

Publication number

AU2002338896B2

AU2002338896B2 AU2002338896A AU2002338896A AU2002338896B2 AU 2002338896 B2 AU2002338896 B2 AU 2002338896B2 AU 2002338896 A AU2002338896 A AU 2002338896A AU 2002338896 A AU2002338896 A AU 2002338896A AU 2002338896 B2 AU2002338896 B2 AU 2002338896B2

Authority

AU

Australia

Prior art keywords

methyl

pyrrolidin

quinolin

quinoline

benzonitrile

Prior art date

2001-05-21

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.)

Ceased

Links

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• 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title claims description 6
• 239000003446 ligand Substances 0.000 title description 7
• 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 3
• 108050002826 Neuropeptide Y Receptor Proteins 0.000 title description 2
• 102000012301 Neuropeptide Y receptor Human genes 0.000 title description 2
• -1 aryl-S0 2 -O-alkcyl Chemical group 0.000 claims description 193
• 238000006243 chemical reaction Methods 0.000 claims description 169
• 150000001875 compounds Chemical class 0.000 claims description 166
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 130
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 117
• 125000000217 alkyl group Chemical group 0.000 claims description 60
• 239000001257 hydrogen Substances 0.000 claims description 56
• 229910052739 hydrogen Inorganic materials 0.000 claims description 56
• 150000002431 hydrogen Chemical group 0.000 claims description 46
• 238000000034 method Methods 0.000 claims description 40
• HTWNTQBDROIOEZ-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-ylquinolin-7-ol Chemical compound C=12C=CC(O)=CC2=NC(C)=CC=1N1CCCC1 HTWNTQBDROIOEZ-UHFFFAOYSA-N 0.000 claims description 39
• 125000003545 alkoxy group Chemical group 0.000 claims description 39
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 38
• 238000011282 treatment Methods 0.000 claims description 36
• 229910052736 halogen Inorganic materials 0.000 claims description 35
• 150000002367 halogens Chemical group 0.000 claims description 35
• 125000003118 aryl group Chemical group 0.000 claims description 31
• 150000003839 salts Chemical class 0.000 claims description 30
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 25
• 208000008589 Obesity Diseases 0.000 claims description 24
• 235000020824 obesity Nutrition 0.000 claims description 24
• 125000000623 heterocyclic group Chemical group 0.000 claims description 23
• 238000011321 prophylaxis Methods 0.000 claims description 23
• 125000003342 alkenyl group Chemical group 0.000 claims description 22
• 125000000304 alkynyl group Chemical group 0.000 claims description 21
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 20
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
• 229940086609 Lipase inhibitor Drugs 0.000 claims description 19
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 19
• 229910052757 nitrogen Inorganic materials 0.000 claims description 19
• 238000002360 preparation method Methods 0.000 claims description 17
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 16
• 206010003246 arthritis Diseases 0.000 claims description 16
• 206010012601 diabetes mellitus Diseases 0.000 claims description 16
• 208000030814 Eating disease Diseases 0.000 claims description 15
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 15
• 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 15
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
• 235000014632 disordered eating Nutrition 0.000 claims description 15
• 239000003814 drug Substances 0.000 claims description 15
• 150000002148 esters Chemical class 0.000 claims description 15
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
• 238000004519 manufacturing process Methods 0.000 claims description 15
• AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical group CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 claims description 15
• 230000008569 process Effects 0.000 claims description 15
• 239000003054 catalyst Substances 0.000 claims description 14
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 14
• 229960001243 orlistat Drugs 0.000 claims description 14
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 13
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
• 125000004104 aryloxy group Chemical group 0.000 claims description 11
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 11
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
• 101710151321 Melanostatin Proteins 0.000 claims description 10
• 102100028427 Pro-neuropeptide Y Human genes 0.000 claims description 10
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
• 239000008194 pharmaceutical composition Substances 0.000 claims description 10
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
• 125000001769 aryl amino group Chemical group 0.000 claims description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
• 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 9
• 229920006395 saturated elastomer Polymers 0.000 claims description 9
• 125000001424 substituent group Chemical group 0.000 claims description 9
• 238000002560 therapeutic procedure Methods 0.000 claims description 9
• CILNSTLMXGWWKH-UHFFFAOYSA-N 6-butyl-4-pyrrolidin-1-ylquinolin-7-ol Chemical compound C1=CN=C2C=C(O)C(CCCC)=CC2=C1N1CCCC1 CILNSTLMXGWWKH-UHFFFAOYSA-N 0.000 claims description 8
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 8
• 238000009833 condensation Methods 0.000 claims description 8
• 230000005494 condensation Effects 0.000 claims description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
• 125000005241 heteroarylamino group Chemical group 0.000 claims description 8
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 7
• 238000006664 bond formation reaction Methods 0.000 claims description 7
• 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 6
• 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 6
• 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 6
• 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 6
• 229910052751 metal Inorganic materials 0.000 claims description 6
• 239000002184 metal Substances 0.000 claims description 6
• 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 5
• 125000003725 azepanyl group Chemical group 0.000 claims description 5
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 5
• 230000002265 prevention Effects 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 4
• 239000013543 active substance Substances 0.000 claims description 4
• 125000001246 bromo group Chemical group Br* 0.000 claims description 4
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
• SRCYQRXUBMEAPQ-UHFFFAOYSA-N 3-[[4-(azepan-1-yl)-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=C(C=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCCCC1 SRCYQRXUBMEAPQ-UHFFFAOYSA-N 0.000 claims description 3
• DPMAQIWJJZJKLV-UHFFFAOYSA-N 4-(azepan-1-yl)-2-methyl-7-(pyridin-4-ylmethoxy)quinoline Chemical compound C=12C=CC(OCC=3C=CN=CC=3)=CC2=NC(C)=CC=1N1CCCCCC1 DPMAQIWJJZJKLV-UHFFFAOYSA-N 0.000 claims description 3
• NHZYJKKSOGTTMR-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 NHZYJKKSOGTTMR-UHFFFAOYSA-N 0.000 claims description 3
• PBVJXDHCRUNAMA-UHFFFAOYSA-N 7-[(2-chloropyridin-3-yl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C(=NC=CC=3)Cl)=CC2=NC(C)=CC=1N1CCCC1 PBVJXDHCRUNAMA-UHFFFAOYSA-N 0.000 claims description 3
• AGTMGARQEGRFBT-UHFFFAOYSA-N 7-[(3-methoxyphenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound COC1=CC=CC(COC=2C=C3N=C(C)C=C(C3=CC=2)N2CCCC2)=C1 AGTMGARQEGRFBT-UHFFFAOYSA-N 0.000 claims description 3
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
• 125000001153 fluoro group Chemical group F* 0.000 claims description 3
• 229910052763 palladium Inorganic materials 0.000 claims description 3
• 125000003884 phenylalkyl group Chemical group 0.000 claims description 3
• 125000006513 pyridinyl methyl group Chemical group 0.000 claims description 3
• 239000004576 sand Substances 0.000 claims description 3
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
• HFVCWXRIRISOEA-UHFFFAOYSA-N 2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C(=CC=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 HFVCWXRIRISOEA-UHFFFAOYSA-N 0.000 claims description 2
• NXANOKNNJGBJJU-UHFFFAOYSA-N 4-[(6-fluoro-2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=12C=C(F)C(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 NXANOKNNJGBJJU-UHFFFAOYSA-N 0.000 claims description 2
• ZLJRLUWCTUDGGW-UHFFFAOYSA-N 4-[[4-(azepan-1-yl)-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCCCC1 ZLJRLUWCTUDGGW-UHFFFAOYSA-N 0.000 claims description 2
• NFLYDVKEEWHEKP-UHFFFAOYSA-N 7-[(3-chlorophenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C=C(Cl)C=CC=3)=CC2=NC(C)=CC=1N1CCCC1 NFLYDVKEEWHEKP-UHFFFAOYSA-N 0.000 claims description 2
• NUXDJOBRDWPOTK-UHFFFAOYSA-N 7-[(4-chlorophenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C=CC(Cl)=CC=3)=CC2=NC(C)=CC=1N1CCCC1 NUXDJOBRDWPOTK-UHFFFAOYSA-N 0.000 claims description 2
• CMHHNHDPPWDNAH-UHFFFAOYSA-N 5'-acetyl-4-{[(2,4-dimethylphenyl)sulfonyl]amino}-2,2'-bithiophene-5-carboxylic acid Chemical compound S1C(C(=O)C)=CC=C1C1=CC(NS(=O)(=O)C=2C(=CC(C)=CC=2)C)=C(C(O)=O)S1 CMHHNHDPPWDNAH-UHFFFAOYSA-N 0.000 claims 1
• 208000035475 disorder Diseases 0.000 claims 1
• 235000005686 eating Nutrition 0.000 claims 1
• 239000007787 solid Substances 0.000 description 177
• 238000001819 mass spectrum Methods 0.000 description 163
• 239000000047 product Substances 0.000 description 125
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 61
• 239000000243 solution Substances 0.000 description 46
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 45
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 30
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 29
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
• 239000002904 solvent Substances 0.000 description 27
• 239000003921 oil Substances 0.000 description 24
• 235000019198 oils Nutrition 0.000 description 24
• 239000012458 free base Substances 0.000 description 23
• 239000000203 mixture Substances 0.000 description 22
• 238000003756 stirring Methods 0.000 description 22
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
• 239000010410 layer Substances 0.000 description 19
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
• 239000011541 reaction mixture Substances 0.000 description 18
• VVVUSVRZYKHWCX-UHFFFAOYSA-N 4-[(4-chloro-2-methylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=1C2=NC(C)=CC(Cl)=C2C=CC=1OCC1=CC=C(C#N)C=C1 VVVUSVRZYKHWCX-UHFFFAOYSA-N 0.000 description 17
• 239000012044 organic layer Substances 0.000 description 16
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
• 235000019341 magnesium sulphate Nutrition 0.000 description 14
• 125000001072 heteroaryl group Chemical group 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 229960004132 diethyl ether Drugs 0.000 description 12
• 238000005984 hydrogenation reaction Methods 0.000 description 11
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
• 238000010992 reflux Methods 0.000 description 11
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
• 239000002585 base Substances 0.000 description 10
• 238000001914 filtration Methods 0.000 description 10
• 238000004128 high performance liquid chromatography Methods 0.000 description 10
• PVSTUKYIRRQGCP-UHFFFAOYSA-N 4-chloro-2-methyl-7-phenylmethoxyquinoline Chemical compound C=1C2=NC(C)=CC(Cl)=C2C=CC=1OCC1=CC=CC=C1 PVSTUKYIRRQGCP-UHFFFAOYSA-N 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 239000012300 argon atmosphere Substances 0.000 description 9
• 125000004432 carbon atom Chemical group C* 0.000 description 9
• 239000003480 eluent Substances 0.000 description 9
• 235000019439 ethyl acetate Nutrition 0.000 description 9
• 229910052760 oxygen Inorganic materials 0.000 description 9
• 239000000741 silica gel Substances 0.000 description 9
• 229910002027 silica gel Inorganic materials 0.000 description 9
• OVZLPAGKKXUGNE-UHFFFAOYSA-N 6-fluoro-2-methyl-4-pyrrolidin-1-ylquinolin-7-ol Chemical compound C=12C=C(F)C(O)=CC2=NC(C)=CC=1N1CCCC1 OVZLPAGKKXUGNE-UHFFFAOYSA-N 0.000 description 8
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
• 208000024172 Cardiovascular disease Diseases 0.000 description 8
• 208000001647 Renal Insufficiency Diseases 0.000 description 8
• 150000001412 amines Chemical class 0.000 description 8
• 238000007429 general method Methods 0.000 description 8
• 201000006370 kidney failure Diseases 0.000 description 8
• 108020003175 receptors Proteins 0.000 description 8
• 102000005962 receptors Human genes 0.000 description 8
• SGSCTTZQIYSSSD-UHFFFAOYSA-N 4-(azepan-1-yl)-2-methylquinolin-7-ol hydrochloride Chemical compound Cl.C=12C=CC(O)=CC2=NC(C)=CC=1N1CCCCCC1 SGSCTTZQIYSSSD-UHFFFAOYSA-N 0.000 description 7
• 125000003282 alkyl amino group Chemical group 0.000 description 7
• 238000004458 analytical method Methods 0.000 description 7
• 239000000706 filtrate Substances 0.000 description 7
• 239000007903 gelatin capsule Substances 0.000 description 7
• 239000005457 ice water Substances 0.000 description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
• MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 6
• GIBRMZKZDBMCTB-ZOWNYOTGSA-N 4-[(3S)-3-ethoxypyrrolidin-1-yl]-2-methylquinolin-7-ol hydrochloride Chemical compound Cl.C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(O)=CC=C12 GIBRMZKZDBMCTB-ZOWNYOTGSA-N 0.000 description 6
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
• 239000002671 adjuvant Substances 0.000 description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
• 239000011203 carbon fibre reinforced carbon 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
• 235000019441 ethanol Nutrition 0.000 description 6
• 125000005842 heteroatom Chemical group 0.000 description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
• 239000007858 starting material Substances 0.000 description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
• DOGYZJVTBGICNB-KRWDZBQOSA-N (3s)-1-(2-methyl-7-phenylmethoxyquinolin-4-yl)pyrrolidin-3-ol Chemical compound C=12C=CC(OCC=3C=CC=CC=3)=CC2=NC(C)=CC=1N1CC[C@H](O)C1 DOGYZJVTBGICNB-KRWDZBQOSA-N 0.000 description 5
• QGXNHCXKWFNKCG-UHFFFAOYSA-N 2-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=CC=C1C#N QGXNHCXKWFNKCG-UHFFFAOYSA-N 0.000 description 5
• PSNCUSAUUATFDT-NSHDSACASA-N 4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-ol Chemical compound C=12C=CC(O)=CC2=NC(C)=CC=1N1CCC[C@H]1CO PSNCUSAUUATFDT-NSHDSACASA-N 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
• 239000002253 acid Substances 0.000 description 5
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 5
• 150000001448 anilines Chemical class 0.000 description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
• 239000012267 brine Substances 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 230000037406 food intake Effects 0.000 description 5
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
• 125000002757 morpholinyl group Chemical group 0.000 description 5
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 5
• 239000001301 oxygen Substances 0.000 description 5
• 229920005862 polyol Polymers 0.000 description 5
• 150000003077 polyols Chemical class 0.000 description 5
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
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