PT99402B - Processo para a preparacao de derivados de imino ciclicos e de composicoes farmaceuticas que os contem - Google Patents

Info

Publication number

PT99402B

PT99402B PT99402A PT9940291A PT99402B PT 99402 B PT99402 B PT 99402B PT 99402 A PT99402 A PT 99402A PT 9940291 A PT9940291 A PT 9940291A PT 99402 B PT99402 B PT 99402B

Authority

PT

Portugal

Prior art keywords

group

alkyl

general formula

substituted

atom

Prior art date

1990-11-02

Links

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• 238000000034 method Methods 0.000 title claims abstract description 24
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 8
• -1 IMINO Chemical class 0.000 title claims description 378
• 101000740162 Homo sapiens Sodium- and chloride-dependent transporter XTRP3 Proteins 0.000 title claims 2
• 102100037189 Sodium- and chloride-dependent transporter XTRP3 Human genes 0.000 title claims 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 205
• 230000008569 process Effects 0.000 claims abstract description 22
• 125000000217 alkyl group Chemical group 0.000 claims description 162
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 160
• 229910052757 nitrogen Inorganic materials 0.000 claims description 159
• 125000003545 alkoxy group Chemical group 0.000 claims description 64
• 229910052799 carbon Inorganic materials 0.000 claims description 64
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 63
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 62
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 61
• 150000001721 carbon Chemical group 0.000 claims description 58
• 239000002253 acid Substances 0.000 claims description 55
• 125000002947 alkylene group Chemical group 0.000 claims description 55
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 48
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 48
• 125000004432 carbon atom Chemical group C* 0.000 claims description 48
• 125000003277 amino group Chemical group 0.000 claims description 40
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 39
• 125000003118 aryl group Chemical group 0.000 claims description 38
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 38
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 37
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 36
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 34
• 238000006243 chemical reaction Methods 0.000 claims description 33
• 125000005842 heteroatom Chemical group 0.000 claims description 32
• 229910052717 sulfur Inorganic materials 0.000 claims description 32
• 125000004122 cyclic group Chemical group 0.000 claims description 31
• 150000003839 salts Chemical class 0.000 claims description 31
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 30
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 28
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 28
• 239000000460 chlorine Substances 0.000 claims description 27
• 229910052801 chlorine Inorganic materials 0.000 claims description 27
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 26
• 229910052760 oxygen Inorganic materials 0.000 claims description 26
• 239000001301 oxygen Substances 0.000 claims description 26
• 125000004434 sulfur atom Chemical group 0.000 claims description 26
• 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 25
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 24
• 150000003951 lactams Chemical group 0.000 claims description 24
• 125000004647 alkyl sulfenyl group Chemical group 0.000 claims description 21
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 21
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 20
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 20
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 19
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 18
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 18
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 18
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 18
• 239000011541 reaction mixture Substances 0.000 claims description 18
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
• 125000000732 arylene group Chemical group 0.000 claims description 17
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
• 239000011737 fluorine Substances 0.000 claims description 16
• 229910052731 fluorine Inorganic materials 0.000 claims description 16
• 239000001257 hydrogen Substances 0.000 claims description 16
• 229910052739 hydrogen Inorganic materials 0.000 claims description 16
• 230000009467 reduction Effects 0.000 claims description 16
• 125000001424 substituent group Chemical group 0.000 claims description 16
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 16
• 125000004429 atom Chemical group 0.000 claims description 15
• 239000002585 base Substances 0.000 claims description 15
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 14
• 125000004646 sulfenyl group Chemical group S(*)* 0.000 claims description 14
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 13
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 13
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• 230000010933 acylation Effects 0.000 claims description 12
• 238000005917 acylation reaction Methods 0.000 claims description 12
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 12
• 125000003282 alkyl amino group Chemical group 0.000 claims description 12
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 12
• 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 12
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
• 125000005567 fluorenylene group Chemical group 0.000 claims description 12
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
• 125000004957 naphthylene group Chemical group 0.000 claims description 12
• 150000007530 organic bases Chemical class 0.000 claims description 12
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 12
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 11
• 150000001412 amines Chemical class 0.000 claims description 11
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 11
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 11
• 229920002554 vinyl polymer Polymers 0.000 claims description 11
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 10
• 150000002148 esters Chemical class 0.000 claims description 10
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 10
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 10
• 238000002360 preparation method Methods 0.000 claims description 10
• 125000006239 protecting group Chemical group 0.000 claims description 10
• 125000005277 alkyl imino group Chemical group 0.000 claims description 9
• 230000029936 alkylation Effects 0.000 claims description 9
• 238000005804 alkylation reaction Methods 0.000 claims description 9
• 125000004467 aryl imino group Chemical group 0.000 claims description 9
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 9
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 9
• 230000003647 oxidation Effects 0.000 claims description 9
• 238000007254 oxidation reaction Methods 0.000 claims description 9
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 9
• HMXQIFUGFZEJEO-UHFFFAOYSA-N 1,2-dihydropyrrol-3-one Chemical group O=C1CNC=C1 HMXQIFUGFZEJEO-UHFFFAOYSA-N 0.000 claims description 8
• 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 8
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 8
• 125000005835 indanylene group Chemical group 0.000 claims description 8
• 150000007529 inorganic bases Chemical class 0.000 claims description 8
• 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 8
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 7
• 125000004185 ester group Chemical group 0.000 claims description 7
• 230000007062 hydrolysis Effects 0.000 claims description 7
• 238000006460 hydrolysis reaction Methods 0.000 claims description 7
• 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 7
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 6
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 6
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 6
• 125000005140 aralkylsulfonyl group Chemical group 0.000 claims description 6
• 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 6
• 125000000638 benzylaminocarbonyl group Chemical group C(C1=CC=CC=C1)NC(=O)* 0.000 claims description 6
• 229910052794 bromium Inorganic materials 0.000 claims description 6
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
• 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 6
• 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 6
• 238000007327 hydrogenolysis reaction Methods 0.000 claims description 6
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 6
• 125000005560 phenanthrenylene group Chemical group 0.000 claims description 6
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
• 125000005208 trialkylammonium group Chemical group 0.000 claims description 6
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 5
• 125000002252 acyl group Chemical group 0.000 claims description 5
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 5
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
• 125000004104 aryloxy group Chemical group 0.000 claims description 5
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
• 229910052740 iodine Inorganic materials 0.000 claims description 5
• 150000007524 organic acids Chemical class 0.000 claims description 5
• 125000002071 phenylalkoxy group Chemical group 0.000 claims description 5
• 230000006103 sulfonylation Effects 0.000 claims description 5
• 238000005694 sulfonylation reaction Methods 0.000 claims description 5
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
• 125000002431 aminoalkoxy group Chemical group 0.000 claims description 4
• 125000005121 aminocarbonylalkoxy group Chemical group 0.000 claims description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
• 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
• 125000001246 bromo group Chemical group Br* 0.000 claims description 4
• ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 4
• 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 claims description 4
• 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 4
• 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 4
• 150000007522 mineralic acids Chemical class 0.000 claims description 4
• 125000001624 naphthyl group Chemical group 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• 235000005985 organic acids Nutrition 0.000 claims description 4
• 125000003884 phenylalkyl group Chemical group 0.000 claims description 4
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
• 239000011593 sulfur Substances 0.000 claims description 4
• 238000001149 thermolysis Methods 0.000 claims description 4
• 238000010306 acid treatment Methods 0.000 claims description 3
• 229910052783 alkali metal Inorganic materials 0.000 claims description 3
• 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
• 125000004414 alkyl thio group Chemical group 0.000 claims description 3
• 150000001409 amidines Chemical class 0.000 claims description 3
• 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 3
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
• 238000007333 cyanation reaction Methods 0.000 claims description 3
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
• 201000010099 disease Diseases 0.000 claims description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
• 125000001153 fluoro group Chemical group F* 0.000 claims description 3
• 230000003993 interaction Effects 0.000 claims description 3
• 239000011159 matrix material Substances 0.000 claims description 3
• 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 3
• 238000005809 transesterification reaction Methods 0.000 claims description 3
• JAVBBFXUGDCHLZ-UHFFFAOYSA-N 1-$l^{1}-oxidanylpropane Chemical compound CCC[O] JAVBBFXUGDCHLZ-UHFFFAOYSA-N 0.000 claims description 2
• RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical group C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 claims description 2
• XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 2
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims description 2
• 238000000297 Sandmeyer reaction Methods 0.000 claims description 2
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-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
• 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 2
• 125000003342 alkenyl group Chemical group 0.000 claims description 2
• 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 2
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 2
• 125000006356 alkylene carbonyl group Chemical group 0.000 claims description 2
• 125000003368 amide group Chemical group 0.000 claims description 2
• 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims description 2
• 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 2
• 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 2
• 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 2
• 125000004997 halocarbonyl group Chemical group 0.000 claims description 2
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
• GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
• UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 2
• 125000004076 pyridyl group Chemical group 0.000 claims description 2
• ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Chemical group C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 claims description 2
• 125000003396 thiol group Chemical class [H]S* 0.000 claims description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical group CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 2
• 125000004417 unsaturated alkyl group Chemical group 0.000 claims description 2
• 239000004480 active ingredient Substances 0.000 claims 2
• VOLGAXAGEUPBDM-UHFFFAOYSA-N $l^{1}-oxidanylethane Chemical compound CC[O] VOLGAXAGEUPBDM-UHFFFAOYSA-N 0.000 claims 1
• OLWVJSRWQNVVNI-UHFFFAOYSA-N [1-[4-(4-carbamimidoylphenyl)phenyl]-5-oxopyrrolidin-3-yl]methylphosphonic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(N2C(CC(CP(O)(O)=O)C2)=O)C=C1 OLWVJSRWQNVVNI-UHFFFAOYSA-N 0.000 claims 1
• 150000001340 alkali metals Chemical class 0.000 claims 1
• 150000001342 alkaline earth metals Chemical class 0.000 claims 1
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims 1
• 125000005126 aryl alkyl carbonyl amino group Chemical group 0.000 claims 1
• 125000004658 aryl carbonyl amino group Chemical group 0.000 claims 1
• 150000005840 aryl radicals Chemical class 0.000 claims 1
• 239000000969 carrier Substances 0.000 claims 1
• 238000001311 chemical methods and process Methods 0.000 claims 1
• 125000005724 cycloalkenylene group Chemical group 0.000 claims 1
• 230000000911 decarboxylating effect Effects 0.000 claims 1
• IKZACQMAVUIGPY-HOTGVXAUSA-N fradafiban Chemical compound C1=CC(C(=N)N)=CC=C1C(C=C1)=CC=C1OC[C@H]1NC(=O)[C@H](CC(O)=O)C1 IKZACQMAVUIGPY-HOTGVXAUSA-N 0.000 claims 1
• 125000004283 imidazolin-2-yl group Chemical group [H]N1C(*)=NC([H])([H])C1([H])[H] 0.000 claims 1
• 239000003701 inert diluent Substances 0.000 claims 1
• 239000004615 ingredient Substances 0.000 claims 1
• YLZHBTAKVXDFGG-UHFFFAOYSA-N methyl 2-(2-oxopyrrolidin-3-yl)acetate Chemical compound COC(=O)CC1CCNC1=O YLZHBTAKVXDFGG-UHFFFAOYSA-N 0.000 claims 1
• 125000005476 oxopyrrolidinyl group Chemical group 0.000 claims 1
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical group O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims 1
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims 1
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims 1
• 230000002776 aggregation Effects 0.000 abstract description 8
• 238000004220 aggregation Methods 0.000 abstract description 8
• 230000002401 inhibitory effect Effects 0.000 abstract description 4
• 230000000144 pharmacologic effect Effects 0.000 abstract description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 481
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 403
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 369
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 279
• 239000000741 silica gel Substances 0.000 description 266
• 229910002027 silica gel Inorganic materials 0.000 description 266
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 169
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 117
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 102
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 99
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 96
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 83
• 239000002904 solvent Substances 0.000 description 83
• 238000002844 melting Methods 0.000 description 82
• 230000008018 melting Effects 0.000 description 82
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 80
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 79
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 72
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