SK282548B6 - Substituované aminoalkánfosfónové kyseliny, spôsob ich prípravy, farmaceutické prostriedky, ktoré ich obsahujú, a ich použitie - Google Patents

Info

Publication number

SK282548B6

SK282548B6 SK523-99A SK52399A SK282548B6 SK 282548 B6 SK282548 B6 SK 282548B6 SK 52399 A SK52399 A SK 52399A SK 282548 B6 SK282548 B6 SK 282548B6

Authority

SK

Slovakia

Prior art keywords

ylmethyl

dioxo

acid

tetrahydroquinoxalin

nitro

Prior art date

1996-10-24

Links

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• 238000002360 preparation method Methods 0.000 title claims abstract description 19
• 239000000825 pharmaceutical preparation Substances 0.000 title abstract 2
• 150000003009 phosphonic acids Chemical class 0.000 title abstract 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 129
• 125000001118 alkylidene group Chemical group 0.000 claims abstract description 72
• 150000003839 salts Chemical class 0.000 claims abstract description 57
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 40
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 30
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 19
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 18
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 18
• 239000001257 hydrogen Substances 0.000 claims abstract description 17
• 125000001931 aliphatic group Chemical group 0.000 claims abstract description 16
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 16
• 150000002367 halogens Chemical class 0.000 claims abstract description 16
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 13
• 125000003118 aryl group Chemical group 0.000 claims abstract description 5
• 230000000903 blocking effect Effects 0.000 claims abstract description 4
• 230000001575 pathological effect Effects 0.000 claims abstract 3
• 239000003814 drug Substances 0.000 claims abstract 2
• -1 aromatic radical Chemical class 0.000 claims description 221
• 239000002253 acid Substances 0.000 claims description 74
• 239000000203 mixture Substances 0.000 claims description 58
• 125000004432 carbon atom Chemical group C* 0.000 claims description 50
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 47
• 125000000217 alkyl group Chemical group 0.000 claims description 45
• 125000002947 alkylene group Chemical group 0.000 claims description 36
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 31
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
• 150000003254 radicals Chemical class 0.000 claims description 19
• 125000006239 protecting group Chemical group 0.000 claims description 18
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
• 150000007513 acids Chemical class 0.000 claims description 15
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 14
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 14
• 238000000034 method Methods 0.000 claims description 13
• 125000003545 alkoxy group Chemical group 0.000 claims description 12
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
• 229910052794 bromium Inorganic materials 0.000 claims description 11
• 229910052799 carbon Inorganic materials 0.000 claims description 11
• 239000000460 chlorine Substances 0.000 claims description 11
• 229910052801 chlorine Inorganic materials 0.000 claims description 11
• 125000004980 cyclopropylene group Chemical group 0.000 claims description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims description 11
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
• 125000001624 naphthyl group Chemical group 0.000 claims description 9
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 7
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 7
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
• GATNOFPXSDHULC-UHFFFAOYSA-N ethylphosphonic acid Chemical compound CCP(O)(O)=O GATNOFPXSDHULC-UHFFFAOYSA-N 0.000 claims description 6
• 125000004957 naphthylene group Chemical group 0.000 claims description 6
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
• MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 claims description 5
• 125000005654 1,2-cyclohexylene group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([*:2])C([H])([*:1])C1([H])[H] 0.000 claims description 5
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
• 102000018899 Glutamate Receptors Human genes 0.000 claims description 5
• 108010027915 Glutamate Receptors Proteins 0.000 claims description 5
• 125000003277 amino group Chemical group 0.000 claims description 5
• 229910052731 fluorine Inorganic materials 0.000 claims description 5
• 239000011737 fluorine Substances 0.000 claims description 5
• 125000005843 halogen group Chemical group 0.000 claims description 5
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
• UYLUJGRCKKSWHS-UHFFFAOYSA-N prop-1-en-1-one Chemical group CC=C=O UYLUJGRCKKSWHS-UHFFFAOYSA-N 0.000 claims description 5
• AYPCRYQYBWTXNP-UHFFFAOYSA-N 2-[(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylamino]propan-2-ylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C([N+]([O-])=O)C=C2CNC(C)(C)P(O)(O)=O AYPCRYQYBWTXNP-UHFFFAOYSA-N 0.000 claims description 4
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
• 239000005977 Ethylene Substances 0.000 claims description 4
• 241001465754 Metazoa Species 0.000 claims description 4
• CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical group C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 claims description 4
• WWQAGDWTJOKFQB-UHFFFAOYSA-N penta-1,2,3-triene Chemical group CC=C=C=C WWQAGDWTJOKFQB-UHFFFAOYSA-N 0.000 claims description 4
• RZGZTQYTDRQOEY-UHFFFAOYSA-N 2-phenylethenone Chemical group O=C=CC1=CC=CC=C1 RZGZTQYTDRQOEY-UHFFFAOYSA-N 0.000 claims description 3
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 3
• 238000003776 cleavage reaction Methods 0.000 claims description 3
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
• 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims description 3
• 230000007017 scission Effects 0.000 claims description 3
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 3
• KCEGUPPDVPWCCX-UHFFFAOYSA-N 6-bromo-1,4-dihydroquinoxaline-2,3-dione Chemical compound C1=C(Br)C=C2N=C(O)C(O)=NC2=C1 KCEGUPPDVPWCCX-UHFFFAOYSA-N 0.000 claims description 2
• DPFHVUSPVHRVFL-YFKPBYRVSA-N CGP 78608 Chemical compound N1C(=O)C(=O)NC2=C1C=C(Br)C=C2CN[C@H](C)P(O)(O)=O DPFHVUSPVHRVFL-YFKPBYRVSA-N 0.000 claims description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
• RDTOXUOEIJUIMX-RXMQYKEDSA-N [(1r)-1-[[2,3-dioxo-7-(trifluoromethyl)-1,4-dihydroquinoxalin-5-yl]methylamino]ethyl]phosphonic acid Chemical compound OC1=C(O)N=C2C(CN[C@@H](C)P(O)(O)=O)=CC(C(F)(F)F)=CC2=N1 RDTOXUOEIJUIMX-RXMQYKEDSA-N 0.000 claims description 2
• FFNKJJGOLMFZKR-UHFFFAOYSA-N [1-[(7-bromo-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylamino]-2-methylpropyl]phosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Br)C=C2CNC(C(C)C)P(O)(O)=O FFNKJJGOLMFZKR-UHFFFAOYSA-N 0.000 claims description 2
• YEDFXUYTNVGXMI-UHFFFAOYSA-N [acetyl-[(7-bromo-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]amino]methylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Br)C=C2CN(C(=O)C)CP(O)(O)=O YEDFXUYTNVGXMI-UHFFFAOYSA-N 0.000 claims description 2
• IGMCOMPQIJDGTG-UHFFFAOYSA-N [acetyl-[(7-chloro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]amino]methylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(Cl)C=C2CN(C(=O)C)CP(O)(O)=O IGMCOMPQIJDGTG-UHFFFAOYSA-N 0.000 claims description 2
• ZSWDXFYLSPZCAS-UHFFFAOYSA-N [acetyl-[(7-fluoro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]amino]methylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C(F)C=C2CN(C(=O)C)CP(O)(O)=O ZSWDXFYLSPZCAS-UHFFFAOYSA-N 0.000 claims description 2
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
• 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• 239000000470 constituent Substances 0.000 claims description 2
• FNIATMYXUPOJRW-UHFFFAOYSA-N cyclohexylidene Chemical group [C]1CCCCC1 FNIATMYXUPOJRW-UHFFFAOYSA-N 0.000 claims description 2
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 2
• AKWJYUMMADUPTI-UHFFFAOYSA-N methyl-[2-[(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylamino]-2-phenylethyl]phosphinic acid Chemical compound C=1C([N+]([O-])=O)=CC=2NC(=O)C(=O)NC=2C=1CNC(CP(O)(=O)C)C1=CC=CC=C1 AKWJYUMMADUPTI-UHFFFAOYSA-N 0.000 claims description 2
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 230000001225 therapeutic effect Effects 0.000 claims description 2
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
• 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims 2
• BPKBZWYRUMZASQ-UHFFFAOYSA-N [2-[(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylamino]phenyl]phosphonic acid Chemical compound OP(O)(=O)C1=CC=CC=C1NCC1=CC([N+]([O-])=O)=CC2=C1NC(=O)C(=O)N2 BPKBZWYRUMZASQ-UHFFFAOYSA-N 0.000 claims 2
• FBWJHGIUUCOZRM-UHFFFAOYSA-N cyclopropylphosphonic acid Chemical compound OP(O)(=O)C1CC1 FBWJHGIUUCOZRM-UHFFFAOYSA-N 0.000 claims 2
• LIOJCWAFYUDVHX-UHFFFAOYSA-N 1-[methyl-[(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]amino]ethylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C([N+]([O-])=O)C=C2CN(C)C(C)P(O)(O)=O LIOJCWAFYUDVHX-UHFFFAOYSA-N 0.000 claims 1
• SYYQEOFYTUZDNR-UHFFFAOYSA-N 2-[(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylamino]butylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C([N+]([O-])=O)C=C2CNC(CP(O)(O)=O)CC SYYQEOFYTUZDNR-UHFFFAOYSA-N 0.000 claims 1
• ULDWFUDJBUUECX-UHFFFAOYSA-N 2-[ethyl-[(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]amino]ethylphosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C([N+]([O-])=O)C=C2CN(CCP(O)(O)=O)CC ULDWFUDJBUUECX-UHFFFAOYSA-N 0.000 claims 1
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
• RNOLFZACEWWIHP-UHFFFAOYSA-N 6-chloro-1,4-dihydroquinoxaline-2,3-dione Chemical compound N1C(=O)C(=O)NC2=CC(Cl)=CC=C21 RNOLFZACEWWIHP-UHFFFAOYSA-N 0.000 claims 1
• RYMLSFWVYNAKAR-UHFFFAOYSA-N 6-nitro-1,4-dihydroquinoxaline-2,3-dione Chemical compound N1C(=O)C(=O)NC2=CC([N+](=O)[O-])=CC=C21 RYMLSFWVYNAKAR-UHFFFAOYSA-N 0.000 claims 1
• VFTOHJFKIJLYKN-UHFFFAOYSA-N 7-nitro-9h-fluoren-2-ol Chemical group [O-][N+](=O)C1=CC=C2C3=CC=C(O)C=C3CC2=C1 VFTOHJFKIJLYKN-UHFFFAOYSA-N 0.000 claims 1
• OHWRASKXEUIFFB-UHFFFAOYSA-N NCP(O)=O Chemical compound NCP(O)=O OHWRASKXEUIFFB-UHFFFAOYSA-N 0.000 claims 1
• MAFWWRJSLIPCQX-UHFFFAOYSA-N O=C1NC2=CC(=CC(=C2NC1=O)CCC(NCC)P(O)(O)=O)[N+](=O)[O-] Chemical compound O=C1NC2=CC(=CC(=C2NC1=O)CCC(NCC)P(O)(O)=O)[N+](=O)[O-] MAFWWRJSLIPCQX-UHFFFAOYSA-N 0.000 claims 1
• RRLCZKWJPVJUSD-UHFFFAOYSA-N [(3-hydroxyphenyl)-[(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylamino]methyl]phosphonic acid Chemical compound OC1=CC=CC(C(NCC=2C=3NC(=O)C(=O)NC=3C=C(C=2)[N+]([O-])=O)P(O)(O)=O)=C1 RRLCZKWJPVJUSD-UHFFFAOYSA-N 0.000 claims 1
• UUIWLVZPDQFCPP-UHFFFAOYSA-N [1-(4-methoxyphenyl)-2-[(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylamino]ethyl]phosphonic acid Chemical compound C1=CC(OC)=CC=C1C(P(O)(O)=O)CNCC1=CC([N+]([O-])=O)=CC2=C1NC(=O)C(=O)N2 UUIWLVZPDQFCPP-UHFFFAOYSA-N 0.000 claims 1
• GZTLDIMDXMFIAC-UHFFFAOYSA-N [1-[(7-bromo-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylamino]cyclopropyl]phosphonic acid Chemical compound C=1C(Br)=CC=2NC(=O)C(=O)NC=2C=1CNC1(P(O)(=O)O)CC1 GZTLDIMDXMFIAC-UHFFFAOYSA-N 0.000 claims 1
• VDHUUTXXAOWEMT-UHFFFAOYSA-N [2-[(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylamino]-3-phenoxypropyl]phosphonic acid Chemical compound C=1C([N+]([O-])=O)=CC=2NC(=O)C(=O)NC=2C=1CNC(CP(O)(=O)O)COC1=CC=CC=C1 VDHUUTXXAOWEMT-UHFFFAOYSA-N 0.000 claims 1
• YKFXIXPHWMHGFH-UHFFFAOYSA-N [2-cyclohexyl-2-[(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylamino]ethyl]phosphonic acid Chemical compound C=1C([N+]([O-])=O)=CC=2NC(=O)C(=O)NC=2C=1CNC(CP(O)(=O)O)C1CCCCC1 YKFXIXPHWMHGFH-UHFFFAOYSA-N 0.000 claims 1
• FRCPMEIRQMUAMA-UHFFFAOYSA-N [2-methoxy-1-[(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylamino]ethyl]phosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C([N+]([O-])=O)C=C2CNC(COC)P(O)(O)=O FRCPMEIRQMUAMA-UHFFFAOYSA-N 0.000 claims 1
• GONNEIKYHFCBGU-UHFFFAOYSA-N [2-methyl-2-[(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylamino]propyl]phosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C([N+]([O-])=O)C=C2CNC(C)(CP(O)(O)=O)C GONNEIKYHFCBGU-UHFFFAOYSA-N 0.000 claims 1
• CYPZMRUQQQRAMY-UHFFFAOYSA-N [3-[(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylamino]-3-oxoprop-1-enyl]phosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C([N+]([O-])=O)C=C2CNC(=O)C=CP(O)(=O)O CYPZMRUQQQRAMY-UHFFFAOYSA-N 0.000 claims 1
• ZADLZIUBGJKARY-UHFFFAOYSA-N [3-methyl-1-[(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylamino]butyl]phosphonic acid Chemical compound N1C(=O)C(=O)NC2=C1C=C([N+]([O-])=O)C=C2CNC(CC(C)C)P(O)(O)=O ZADLZIUBGJKARY-UHFFFAOYSA-N 0.000 claims 1
• XBNSDEAMAMVBJN-UHFFFAOYSA-N [benzyl-[(7-chloro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]amino]methylphosphonic acid Chemical compound C=1C(Cl)=CC=2NC(=O)C(=O)NC=2C=1CN(CP(O)(=O)O)CC1=CC=CC=C1 XBNSDEAMAMVBJN-UHFFFAOYSA-N 0.000 claims 1
• 229940058182 aminoethylphosphinic acid Drugs 0.000 claims 1
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
• 125000003884 phenylalkyl group Chemical group 0.000 claims 1
• 150000001413 amino acids Chemical class 0.000 abstract 1
• 150000002431 hydrogen Chemical class 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 52
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
• 235000002639 sodium chloride Nutrition 0.000 description 48
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
• 238000002844 melting Methods 0.000 description 42
• 230000008018 melting Effects 0.000 description 42
• 238000000354 decomposition reaction Methods 0.000 description 39
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
• 239000000243 solution Substances 0.000 description 32
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
• 238000005160 1H NMR spectroscopy Methods 0.000 description 27
• 239000011541 reaction mixture Substances 0.000 description 27
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
• 239000013078 crystal Substances 0.000 description 19
• 239000007787 solid Substances 0.000 description 19
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
• 239000012074 organic phase Substances 0.000 description 18
• 239000002585 base Substances 0.000 description 17
• 239000007858 starting material Substances 0.000 description 17
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
• 235000019341 magnesium sulphate Nutrition 0.000 description 15
• 125000004043 oxo group Chemical group O=* 0.000 description 15
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
• 239000004480 active ingredient Substances 0.000 description 14
• 239000012267 brine Substances 0.000 description 14
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 13
• 238000010992 reflux Methods 0.000 description 13
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