CA2023229A1

CA2023229A1 - Composes azotes

Composes azotes

Info

Publication number: CA2023229A1
Authority: CA; Canada
Prior art keywords: ethyl; formula; quinoline; tetrazol; methoxy
Prior art date: 1989-08-11
Legal status : Abandoned

Application number

CA 2023229

Other languages

English (en)

Inventor

David Anthony Roberts

Simon Thomas Russell

Robert James Pearce

Current Assignee

Imperial Chemical Industries Ltd

Original Assignee

Individual

Priority date

1989-08-11

Filing date

1990-08-02

Publication date

1991-02-12

1990-08-02 Application filed by Individual filed Critical Individual

1990-08-02 Priority to CA 2023229 priority Critical patent/CA2023229A1/fr

1991-02-12 Publication of CA2023229A1 publication Critical patent/CA2023229A1/fr

Status Abandoned legal-status Critical Current

Links

229910017464 nitrogen compound Inorganic materials 0.000 title abstract 2
150000002830 nitrogen compounds Chemical class 0.000 title abstract 2
150000001875 compounds Chemical class 0.000 claims abstract description 100
238000000034 method Methods 0.000 claims abstract description 36
150000003839 salts Chemical class 0.000 claims abstract description 33
231100000252 nontoxic Toxicity 0.000 claims abstract description 16
230000003000 nontoxic effect Effects 0.000 claims abstract description 16
238000011282 treatment Methods 0.000 claims abstract description 8
238000004519 manufacturing process Methods 0.000 claims abstract description 6
230000008569 process Effects 0.000 claims abstract description 6
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
-1 cyano, nitro, phenyl Chemical group 0.000 claims description 112
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 84
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 66
125000000217 alkyl group Chemical group 0.000 claims description 39
239000000203 mixture Substances 0.000 claims description 39
239000001257 hydrogen Substances 0.000 claims description 35
229910052739 hydrogen Inorganic materials 0.000 claims description 35
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 27
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
238000006243 chemical reaction Methods 0.000 claims description 21
239000002253 acid Substances 0.000 claims description 19
125000003545 alkoxy group Chemical group 0.000 claims description 19
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
125000005843 halogen group Chemical group 0.000 claims description 15
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
125000001424 substituent group Chemical group 0.000 claims description 14
125000004432 carbon atom Chemical group C* 0.000 claims description 13
125000004093 cyano group Chemical group *C#N 0.000 claims description 13
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
239000007858 starting material Substances 0.000 claims description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
229910052783 alkali metal Inorganic materials 0.000 claims description 12
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
125000000753 cycloalkyl group Chemical group 0.000 claims description 12
239000002585 base Substances 0.000 claims description 11
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
125000001153 fluoro group Chemical group F* 0.000 claims description 9
230000002378 acidificating effect Effects 0.000 claims description 8
239000003085 diluting agent Substances 0.000 claims description 8
150000002431 hydrogen Chemical group 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
125000001309 chloro group Chemical group Cl* 0.000 claims description 7
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
150000007513 acids Chemical class 0.000 claims description 5
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
230000015572 biosynthetic process Effects 0.000 claims description 5
125000001246 bromo group Chemical group Br* 0.000 claims description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
150000007530 organic bases Chemical class 0.000 claims description 5
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 5
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 5
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 5
150000003248 quinolines Chemical class 0.000 claims description 5
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 4
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 4
150000001340 alkali metals Chemical class 0.000 claims description 4
125000005236 alkanoylamino group Chemical group 0.000 claims description 4
125000003282 alkyl amino group Chemical group 0.000 claims description 4
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
125000004414 alkyl thio group Chemical group 0.000 claims description 4
125000005530 alkylenedioxy group Chemical group 0.000 claims description 4
150000001450 anions Chemical class 0.000 claims description 4
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 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
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 4
125000004663 dialkyl amino group Chemical group 0.000 claims description 4
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
125000003831 tetrazolyl group Chemical group 0.000 claims description 4
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
125000001589 carboacyl group Chemical group 0.000 claims description 3
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
150000002440 hydroxy compounds Chemical class 0.000 claims description 3
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 3
150000002825 nitriles Chemical class 0.000 claims description 3
125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 3
125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 3
125000006239 protecting group Chemical group 0.000 claims description 3
SMUQFGGVLNAIOZ-UHFFFAOYSA-N quinaldine Chemical compound C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 claims description 3
LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 3
FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 claims description 3
229940124530 sulfonamide Drugs 0.000 claims description 3
NXHLTRRJYMDMHC-UHFFFAOYSA-N (2-ethylquinolin-6-yl)methanamine Chemical compound C1=C(CN)C=CC2=NC(CC)=CC=C21 NXHLTRRJYMDMHC-UHFFFAOYSA-N 0.000 claims description 2
XUBKQWYBWKSYNC-UHFFFAOYSA-N (2-ethylquinolin-7-yl)methanol Chemical compound C1=CC(CO)=CC2=NC(CC)=CC=C21 XUBKQWYBWKSYNC-UHFFFAOYSA-N 0.000 claims description 2
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 2
UFMAOAQSWIMXPH-UHFFFAOYSA-N 2-ethyl-5,6,7-trimethoxyquinoline Chemical compound COC1=C(OC)C(OC)=CC2=NC(CC)=CC=C21 UFMAOAQSWIMXPH-UHFFFAOYSA-N 0.000 claims description 2
VAHCQIPIEIFFLV-UHFFFAOYSA-N 2-ethyl-6,7-dimethoxyquinoline Chemical compound C1=C(OC)C(OC)=CC2=NC(CC)=CC=C21 VAHCQIPIEIFFLV-UHFFFAOYSA-N 0.000 claims description 2
JADILNVCQNJGSC-UHFFFAOYSA-N 2-ethyl-6-(2,2,2-trifluoroethoxy)quinoline Chemical compound C1=C(OCC(F)(F)F)C=CC2=NC(CC)=CC=C21 JADILNVCQNJGSC-UHFFFAOYSA-N 0.000 claims description 2
DLTPRYGIIBGYCM-UHFFFAOYSA-N 2-ethyl-6-(2-fluoroethoxy)quinoline Chemical compound C1=C(OCCF)C=CC2=NC(CC)=CC=C21 DLTPRYGIIBGYCM-UHFFFAOYSA-N 0.000 claims description 2
LKVGOJUQDXXVEE-UHFFFAOYSA-N 2-ethyl-6-methoxyquinoline Chemical compound C1=C(OC)C=CC2=NC(CC)=CC=C21 LKVGOJUQDXXVEE-UHFFFAOYSA-N 0.000 claims description 2
DSSYCNGGYDHPMB-UHFFFAOYSA-N 2-ethyl-6-methylsulfanylquinoline Chemical compound C1=C(SC)C=CC2=NC(CC)=CC=C21 DSSYCNGGYDHPMB-UHFFFAOYSA-N 0.000 claims description 2
MSCYXPWZCOHWQV-UHFFFAOYSA-N 2-ethyl-6-propan-2-yloxyquinoline Chemical compound C1=C(OC(C)C)C=CC2=NC(CC)=CC=C21 MSCYXPWZCOHWQV-UHFFFAOYSA-N 0.000 claims description 2
MIHWHMRWXQEAGH-UHFFFAOYSA-N 2-ethylquinolin-6-ol Chemical compound C1=C(O)C=CC2=NC(CC)=CC=C21 MIHWHMRWXQEAGH-UHFFFAOYSA-N 0.000 claims description 2
XCIZVKSCLVSDHN-UHFFFAOYSA-N 2-ethylquinoline Chemical compound C1=CC=CC2=NC(CC)=CC=C21 XCIZVKSCLVSDHN-UHFFFAOYSA-N 0.000 claims description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
150000001342 alkaline earth metals Chemical class 0.000 claims description 2
239000004411 aluminium Substances 0.000 claims description 2
229910052782 aluminium Inorganic materials 0.000 claims description 2
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 2
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
150000003863 ammonium salts Chemical class 0.000 claims description 2
150000001540 azides Chemical class 0.000 claims description 2
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
150000002500 ions Chemical class 0.000 claims description 2
KXOLPQKEBWRMAZ-UHFFFAOYSA-N methyl 4-[(2-methoxycarbonylphenyl)methoxy]quinoline-3-carboxylate Chemical compound COC(=O)C1=CC=CC=C1COC1=C(C(=O)OC)C=NC2=CC=CC=C12 KXOLPQKEBWRMAZ-UHFFFAOYSA-N 0.000 claims description 2
229910052757 nitrogen Inorganic materials 0.000 claims description 2
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 2
238000000926 separation method Methods 0.000 claims description 2
FSJCYXPMWQPVOS-UHFFFAOYSA-N 2-ethyl-4-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methoxy]quinoline Chemical compound C=12C=CC=CC2=NC(CC)=CC=1OCC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 FSJCYXPMWQPVOS-UHFFFAOYSA-N 0.000 claims 2
RCLGGIAMMVTFHF-UHFFFAOYSA-N 2-ethyl-4-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methoxy]-6-(2,2,2-trifluoroethoxy)quinoline Chemical compound C=12C=C(OCC(F)(F)F)C=CC2=NC(CC)=CC=1OCC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 RCLGGIAMMVTFHF-UHFFFAOYSA-N 0.000 claims 1
IGGLDYAOSSEPJI-UHFFFAOYSA-N 2-ethyl-4-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methoxy]quinoline-6-carbonitrile Chemical compound C=12C=C(C#N)C=CC2=NC(CC)=CC=1OCC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 IGGLDYAOSSEPJI-UHFFFAOYSA-N 0.000 claims 1
KDCSKSAHCRQYQE-UHFFFAOYSA-N 2-ethyl-6,8-dimethyl-4-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methoxy]quinoline Chemical compound C=12C=C(C)C=C(C)C2=NC(CC)=CC=1OCC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 KDCSKSAHCRQYQE-UHFFFAOYSA-N 0.000 claims 1
ALVFJERTMZQZLM-UHFFFAOYSA-N 2-ethyl-6-fluoro-4-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methoxy]quinoline Chemical compound C=12C=C(F)C=CC2=NC(CC)=CC=1OCC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 ALVFJERTMZQZLM-UHFFFAOYSA-N 0.000 claims 1
MJLRQHITGCIWMF-UHFFFAOYSA-N 2-ethyl-6-fluoroquinoline Chemical compound C1=C(F)C=CC2=NC(CC)=CC=C21 MJLRQHITGCIWMF-UHFFFAOYSA-N 0.000 claims 1
RVOVQMXVIYSHDX-UHFFFAOYSA-N 2-ethyl-6-methylsulfanyl-4-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methoxy]quinoline Chemical compound C=12C=C(SC)C=CC2=NC(CC)=CC=1OCC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 RVOVQMXVIYSHDX-UHFFFAOYSA-N 0.000 claims 1
WKPMEBRCZJUODK-UHFFFAOYSA-N 2-ethyl-6-propan-2-yloxy-4-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methoxy]quinoline Chemical compound C=12C=C(OC(C)C)C=CC2=NC(CC)=CC=1OCC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 WKPMEBRCZJUODK-UHFFFAOYSA-N 0.000 claims 1
VEUWFLRDJJOYHX-UHFFFAOYSA-N [2-ethyl-4-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methoxy]quinolin-6-yl]methanamine Chemical compound C=12C=C(CN)C=CC2=NC(CC)=CC=1OCC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 VEUWFLRDJJOYHX-UHFFFAOYSA-N 0.000 claims 1
ZIHWIFNYKYOJAE-UHFFFAOYSA-N [2-ethyl-4-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methoxy]quinolin-7-yl]methanol Chemical compound C=12C=CC(CO)=CC2=NC(CC)=CC=1OCC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 ZIHWIFNYKYOJAE-UHFFFAOYSA-N 0.000 claims 1
206010020772 Hypertension Diseases 0.000 abstract description 4
206010007559 Cardiac failure congestive Diseases 0.000 abstract description 3
206010019280 Heart failures Diseases 0.000 abstract description 3
238000005481 NMR spectroscopy Methods 0.000 description 111
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 65
238000004452 microanalysis Methods 0.000 description 63
238000001819 mass spectrum Methods 0.000 description 57
125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 52
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 51
239000000243 solution Substances 0.000 description 51
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 37
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 35
238000012360 testing method Methods 0.000 description 29
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
239000007787 solid Substances 0.000 description 25
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 24
229910000041 hydrogen chloride Inorganic materials 0.000 description 24
PSXRWZBTVAZNSF-UHFFFAOYSA-N hydron;quinoline;chloride Chemical compound Cl.N1=CC=CC2=CC=CC=C21 PSXRWZBTVAZNSF-UHFFFAOYSA-N 0.000 description 23
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 22
235000019439 ethyl acetate Nutrition 0.000 description 22
239000002904 solvent Substances 0.000 description 19
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
239000006260 foam Substances 0.000 description 17
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
238000001704 evaporation Methods 0.000 description 13
230000008020 evaporation Effects 0.000 description 13
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
238000003818 flash chromatography Methods 0.000 description 12
241001465754 Metazoa Species 0.000 description 10
229910052943 magnesium sulfate Inorganic materials 0.000 description 10
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241000282414 Homo sapiens Species 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
201000010099 disease Diseases 0.000 description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
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DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
230000009471 action Effects 0.000 description 7
238000001914 filtration Methods 0.000 description 7
230000000144 pharmacologic effect Effects 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
102000015427 Angiotensins Human genes 0.000 description 6
108010064733 Angiotensins Proteins 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
125000001743 benzylic group Chemical group 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
238000006460 hydrolysis reaction Methods 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
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239000012312 sodium hydride Substances 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
239000000463 material Substances 0.000 description 5
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150000007660 quinolones Chemical class 0.000 description 5
238000010992 reflux Methods 0.000 description 5
230000036454 renin-angiotensin system Effects 0.000 description 5
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