HU200338B - Process for producing 4-square brackets open /bicyclic-heterocyclic/-methyl- and hetero square brackets closed-piperidines and pharmaceutical compositions comprising same - Google Patents

Info

Publication number

HU200338B

HU200338B HU8561A HU6185A HU200338B HU 200338 B HU200338 B HU 200338B HU 8561 A HU8561 A HU 8561A HU 6185 A HU6185 A HU 6185A HU 200338 B HU200338 B HU 200338B

Authority

HU

Hungary

Prior art keywords

formula

methyl

compound

parts

weight

Prior art date

1984-01-09

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• 238000000034 method Methods 0.000 title claims abstract description 27
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
• 125000002618 bicyclic heterocycle group Chemical group 0.000 title claims abstract description 5
• 125000005842 heteroatom Chemical group 0.000 title claims description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 286
• 150000001875 compounds Chemical class 0.000 claims abstract description 237
• 150000003839 salts Chemical class 0.000 claims abstract description 160
• 239000002253 acid Substances 0.000 claims abstract description 45
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 23
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 22
• 239000004480 active ingredient Substances 0.000 claims abstract description 17
• -1 dimethylaminocarbonyl Chemical group 0.000 claims description 193
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 62
• 239000002585 base Substances 0.000 claims description 60
• 229910052739 hydrogen Inorganic materials 0.000 claims description 42
• 239000001257 hydrogen Substances 0.000 claims description 42
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 36
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 35
• 125000000217 alkyl group Chemical group 0.000 claims description 33
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 32
• 238000006243 chemical reaction Methods 0.000 claims description 30
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 28
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
• 239000002904 solvent Substances 0.000 claims description 26
• 125000001424 substituent group Chemical group 0.000 claims description 25
• 239000003054 catalyst Substances 0.000 claims description 21
• 229910052736 halogen Inorganic materials 0.000 claims description 21
• 239000001301 oxygen Substances 0.000 claims description 21
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 19
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 19
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
• 239000011593 sulfur Substances 0.000 claims description 18
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
• 125000004432 carbon atom Chemical group C* 0.000 claims description 17
• 238000002360 preparation method Methods 0.000 claims description 16
• 239000007858 starting material Substances 0.000 claims description 15
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 14
• 125000005843 halogen group Chemical group 0.000 claims description 14
• 239000012442 inert solvent Substances 0.000 claims description 14
• 239000003153 chemical reaction reagent Substances 0.000 claims description 13
• 150000003053 piperidines Chemical class 0.000 claims description 13
• 150000002367 halogens Chemical class 0.000 claims description 10
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 9
• 239000007864 aqueous solution Substances 0.000 claims description 9
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 9
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
• 238000007126 N-alkylation reaction Methods 0.000 claims description 8
• 125000003545 alkoxy group Chemical group 0.000 claims description 8
• 150000001412 amines Chemical class 0.000 claims description 8
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
• 150000002576 ketones Chemical class 0.000 claims description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
• 125000004429 atom Chemical group 0.000 claims description 6
• 239000004202 carbamide Substances 0.000 claims description 6
• 229910052799 carbon Inorganic materials 0.000 claims description 6
• 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 6
• 150000002431 hydrogen Chemical class 0.000 claims description 6
• 238000005984 hydrogenation reaction Methods 0.000 claims description 6
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 6
• 230000002829 reductive effect Effects 0.000 claims description 6
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 5
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 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
• 239000003795 chemical substances by application Substances 0.000 claims description 5
• 150000002148 esters Chemical class 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 238000007254 oxidation reaction Methods 0.000 claims description 5
• 125000000335 thiazolyl group Chemical group 0.000 claims description 5
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 4
• 101150065749 Churc1 gene Proteins 0.000 claims description 4
• 102100038239 Protein Churchill Human genes 0.000 claims description 4
• 229910052783 alkali metal Inorganic materials 0.000 claims description 4
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
• 239000012458 free base Substances 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 claims description 4
• 125000001624 naphthyl group Chemical group 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 4
• 125000004434 sulfur atom Chemical group 0.000 claims description 4
• 125000001544 thienyl group Chemical group 0.000 claims description 4
• ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 claims description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
• 150000008065 acid anhydrides Chemical class 0.000 claims description 3
• 150000001340 alkali metals Chemical group 0.000 claims description 3
• 239000012736 aqueous medium Substances 0.000 claims description 3
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
• 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000002541 furyl group Chemical group 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 229910052757 nitrogen Inorganic materials 0.000 claims description 3
• 230000003647 oxidation Effects 0.000 claims description 3
• 239000000843 powder Substances 0.000 claims description 3
• 238000006798 ring closing metathesis reaction Methods 0.000 claims description 3
• 239000000126 substance Substances 0.000 claims description 3
• 239000000758 substrate Substances 0.000 claims description 3
• YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims description 2
• JMTMWFZXOIWTLX-UHFFFAOYSA-N 2-pyridin-2-yloxypyridine Chemical group C=1C=CC=NC=1OC1=CC=CC=N1 JMTMWFZXOIWTLX-UHFFFAOYSA-N 0.000 claims description 2
• 125000006418 4-methylphenylsulfonyl group Chemical group 0.000 claims description 2
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 2
• 150000001336 alkenes Chemical class 0.000 claims description 2
• 125000003342 alkenyl group Chemical group 0.000 claims description 2
• 125000003282 alkyl amino group Chemical group 0.000 claims description 2
• 125000004414 alkyl thio group Chemical group 0.000 claims description 2
• 150000004985 diamines Chemical class 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 229910044991 metal oxide Inorganic materials 0.000 claims description 2
• 150000004706 metal oxides Chemical class 0.000 claims description 2
• 125000002757 morpholinyl group Chemical group 0.000 claims description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
• 231100000252 nontoxic Toxicity 0.000 claims description 2
• 230000003000 nontoxic effect Effects 0.000 claims description 2
• 150000002978 peroxides Chemical class 0.000 claims description 2
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 2
• 229920006324 polyoxymethylene Polymers 0.000 claims description 2
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
• 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
• 230000009466 transformation Effects 0.000 claims description 2
• 238000000844 transformation Methods 0.000 claims description 2
• 230000002378 acidificating effect Effects 0.000 claims 3
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 3
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims 2
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims 2
• 150000001408 amides Chemical class 0.000 claims 2
• 150000001735 carboxylic acids Chemical class 0.000 claims 2
• JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims 2
• 230000003301 hydrolyzing effect Effects 0.000 claims 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims 2
• 150000003556 thioamides Chemical class 0.000 claims 2
• SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 claims 1
• 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims 1
• 150000001351 alkyl iodides Chemical class 0.000 claims 1
• 230000002152 alkylating effect Effects 0.000 claims 1
• 230000006315 carbonylation Effects 0.000 claims 1
• 238000005810 carbonylation reaction Methods 0.000 claims 1
• 229940125904 compound 1 Drugs 0.000 claims 1
• 125000000753 cycloalkyl group Chemical group 0.000 claims 1
• 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 1
• 238000005695 dehalogenation reaction Methods 0.000 claims 1
• 150000003948 formamides Chemical class 0.000 claims 1
• 235000019253 formic acid Nutrition 0.000 claims 1
• 150000002357 guanidines Chemical class 0.000 claims 1
• 125000001041 indolyl group Chemical group 0.000 claims 1
• 239000013067 intermediate product Substances 0.000 claims 1
• 239000002609 medium Substances 0.000 claims 1
• WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims 1
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 1
• 210000003205 muscle Anatomy 0.000 claims 1
• 125000006678 phenoxycarbonyl group Chemical group 0.000 claims 1
• 108090000623 proteins and genes Proteins 0.000 claims 1
• 125000003396 thiol group Chemical group [H]S* 0.000 claims 1
• 150000003585 thioureas Chemical class 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 175
• 239000000043 antiallergic agent Substances 0.000 abstract 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 226
• 239000000047 product Substances 0.000 description 155
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 146
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 134
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 125
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 99
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 94
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 76
• 238000003756 stirring Methods 0.000 description 71
• 125000000896 monocarboxylic acid group Chemical group 0.000 description 67
• 239000000243 solution Substances 0.000 description 63
• 229960001701 chloroform Drugs 0.000 description 60
• 239000011541 reaction mixture Substances 0.000 description 59
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 53
• 239000000543 intermediate Substances 0.000 description 50
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 45
• KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 43
• 239000003480 eluent Substances 0.000 description 41
• 239000000284 extract Substances 0.000 description 41
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 38
• IDRUFHLMTBZQBT-NSCUHMNNSA-N 2-[(e)-prop-1-enyl]propanedioic acid Chemical compound C\C=C\C(C(O)=O)C(O)=O IDRUFHLMTBZQBT-NSCUHMNNSA-N 0.000 description 37
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 35
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 34
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 33
• 239000000706 filtrate Substances 0.000 description 29
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 28
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
• 238000010992 reflux Methods 0.000 description 25
• KBIWNQVZKHSHTI-UHFFFAOYSA-N 4-n,4-n-dimethylbenzene-1,4-diamine;oxalic acid Chemical compound OC(=O)C(O)=O.CN(C)C1=CC=C(N)C=C1 KBIWNQVZKHSHTI-UHFFFAOYSA-N 0.000 description 24
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 24
• 229920006395 saturated elastomer Polymers 0.000 description 24
• 239000000741 silica gel Substances 0.000 description 24
• 229910002027 silica gel Inorganic materials 0.000 description 24
• 229910021529 ammonia Inorganic materials 0.000 description 23
• 238000002844 melting Methods 0.000 description 23
• NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 21
• UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 21
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• 230000008018 melting Effects 0.000 description 19
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 18
• 239000000908 ammonium hydroxide Substances 0.000 description 18
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 18
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 18
• 241000700159 Rattus Species 0.000 description 16
• 238000004440 column chromatography Methods 0.000 description 16
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 15
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 15
• 238000010898 silica gel chromatography Methods 0.000 description 15
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 14
• 150000004682 monohydrates Chemical class 0.000 description 14
• 229910000029 sodium carbonate Inorganic materials 0.000 description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 12
• 229960000583 acetic acid Drugs 0.000 description 11
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 10
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 10
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 10
• 239000012312 sodium hydride Substances 0.000 description 10
• 229910000104 sodium hydride Inorganic materials 0.000 description 10
• 125000004149 thio group Chemical group *S* 0.000 description 10
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 9
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
• 235000011054 acetic acid Nutrition 0.000 description 9
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 8
• 239000006185 dispersion Substances 0.000 description 8
• 150000008282 halocarbons Chemical class 0.000 description 8
• 239000012074 organic phase Substances 0.000 description 8
• 239000003826 tablet Substances 0.000 description 8
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 8
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 7
• 235000011121 sodium hydroxide Nutrition 0.000 description 7
• 210000002784 stomach Anatomy 0.000 description 7
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 6
• 239000004215 Carbon black (E152) Substances 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• 239000000739 antihistaminic agent Substances 0.000 description 6
• 239000003420 antiserotonin agent Substances 0.000 description 6
• 238000000605 extraction Methods 0.000 description 6
• 229930195733 hydrocarbon Natural products 0.000 description 6
• 150000002430 hydrocarbons Chemical class 0.000 description 6
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
• 239000007787 solid Substances 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
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