BE478523A

BE478523A -

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Publication number: BE478523A
Authority: BE; Belgium
Prior art keywords: methyl; imidazolidone; phenyl; hydrogenated; group
Prior art date

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English (en)

French (fr)

Publication of BE478523A publication Critical patent/BE478523A/fr

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150000001875 compounds Chemical class 0.000 claims description 23
238000005984 hydrogenation reaction Methods 0.000 claims description 20
YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 claims description 17
239000003054 catalyst Substances 0.000 claims description 14
150000004985 diamines Chemical class 0.000 claims description 12
238000000034 method Methods 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 10
-1 3,4-dibenzyloxyphenyl Chemical group 0.000 claims description 9
230000007062 hydrolysis Effects 0.000 claims description 9
238000006460 hydrolysis reaction Methods 0.000 claims description 9
150000003839 salts Chemical class 0.000 claims description 7
CAAMSDWKXXPUJR-UHFFFAOYSA-N 3,5-dihydro-4H-imidazol-4-one Chemical compound O=C1CNC=N1 CAAMSDWKXXPUJR-UHFFFAOYSA-N 0.000 claims description 6
IEOVAZVJCNUJPI-UHFFFAOYSA-N 1-phenylbutane-2,3-diamine Chemical compound CC(N)C(N)CC1=CC=CC=C1 IEOVAZVJCNUJPI-UHFFFAOYSA-N 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 4
125000000217 alkyl group Chemical group 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
230000002378 acidificating effect Effects 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical group [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 3
KBCCFPQJYAZWGA-UHFFFAOYSA-N 3,4-dimethyl-5-phenyl-1h-imidazol-2-one Chemical compound N1C(=O)N(C)C(C)=C1C1=CC=CC=C1 KBCCFPQJYAZWGA-UHFFFAOYSA-N 0.000 claims description 2
125000003710 aryl alkyl group Chemical group 0.000 claims 3
125000003118 aryl group Chemical group 0.000 claims 3
ISIJGZLHZALNDU-UHFFFAOYSA-N 2-n-methyl-1-phenylpropane-1,2-diamine Chemical compound CNC(C)C(N)C1=CC=CC=C1 ISIJGZLHZALNDU-UHFFFAOYSA-N 0.000 claims 1
239000003795 chemical substances by application Substances 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
229910052751 metal Inorganic materials 0.000 claims 1
239000002184 metal Substances 0.000 claims 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 79
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 75
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 50
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 49
238000002844 melting Methods 0.000 description 49
230000008018 melting Effects 0.000 description 49
239000000243 solution Substances 0.000 description 41
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
239000000203 mixture Substances 0.000 description 29
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 23
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
239000013078 crystal Substances 0.000 description 21
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 20
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
229960000583 acetic acid Drugs 0.000 description 17
238000010992 reflux Methods 0.000 description 15
239000000126 substance Substances 0.000 description 12
239000000047 product Substances 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
239000001257 hydrogen Substances 0.000 description 9
239000000155 melt Substances 0.000 description 9
230000001476 alcoholic effect Effects 0.000 description 8
238000009835 boiling Methods 0.000 description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
238000001816 cooling Methods 0.000 description 6
239000012043 crude product Substances 0.000 description 6
238000002425 crystallisation Methods 0.000 description 6
230000008025 crystallization Effects 0.000 description 6
230000001376 precipitating effect Effects 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
238000000859 sublimation Methods 0.000 description 6
230000008022 sublimation Effects 0.000 description 6
WZELXJBMMZFDDU-UHFFFAOYSA-N Imidazol-2-one Chemical class O=C1N=CC=N1 WZELXJBMMZFDDU-UHFFFAOYSA-N 0.000 description 5
239000003921 oil Substances 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
238000004090 dissolution Methods 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
239000007788 liquid Substances 0.000 description 4
GSQBXSXDPQFFOT-UHFFFAOYSA-N 4-(cyclohexylmethyl)imidazolidin-2-one Chemical compound C1(CCCCC1)CC1NC(NC1)=O GSQBXSXDPQFFOT-UHFFFAOYSA-N 0.000 description 3
WLRPOQVNDMDZEV-UHFFFAOYSA-N 4-benzoyl-5-methylimidazol-2-one Chemical compound CC1=NC(=O)N=C1C(=O)C1=CC=CC=C1 WLRPOQVNDMDZEV-UHFFFAOYSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
230000021736 acetylation Effects 0.000 description 3
238000006640 acetylation reaction Methods 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 description 3
239000012299 nitrogen atmosphere Substances 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 3
238000001556 precipitation Methods 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
239000000725 suspension Substances 0.000 description 3
VWFITDMAWXMPQO-UHFFFAOYSA-N 1,3-diacetyl-4-benzoyl-5-methylimidazol-2-one Chemical compound CC(=O)N1C(=O)N(C(=O)C)C(C)=C1C(=O)C1=CC=CC=C1 VWFITDMAWXMPQO-UHFFFAOYSA-N 0.000 description 2
BGPAZBKCZVVZGF-UHFFFAOYSA-N 1,5-dimethyl-4-phenylimidazolidin-2-one Chemical compound N1C(=O)N(C)C(C)C1C1=CC=CC=C1 BGPAZBKCZVVZGF-UHFFFAOYSA-N 0.000 description 2
LRNGDEHBVKSHOV-UHFFFAOYSA-N 1-cyclohexylbutane-2,3-diamine Chemical compound CC(N)C(N)CC1CCCCC1 LRNGDEHBVKSHOV-UHFFFAOYSA-N 0.000 description 2
ONZDMLLPTPDQAT-UHFFFAOYSA-N 3-phenylpropane-1,2-diamine;dihydrochloride Chemical compound Cl.Cl.NCC(N)CC1=CC=CC=C1 ONZDMLLPTPDQAT-UHFFFAOYSA-N 0.000 description 2
ITCUMICAEDFLIL-UHFFFAOYSA-N 4-benzoylimidazol-2-one Chemical compound C=1C=CC=CC=1C(=O)C1=NC(=O)N=C1 ITCUMICAEDFLIL-UHFFFAOYSA-N 0.000 description 2
IAJWRZNYVRNODU-UHFFFAOYSA-N 4-benzyl-5-methylimidazol-2-one Chemical compound CC1=NC(=O)N=C1CC1=CC=CC=C1 IAJWRZNYVRNODU-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
239000002253 acid Substances 0.000 description 2
239000003513 alkali Substances 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
229940073608 benzyl chloride Drugs 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
150000002431 hydrogen Chemical class 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
AGJSNMGHAVDLRQ-HUUJSLGLSA-N methyl (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-HUUJSLGLSA-N 0.000 description 2
239000012452 mother liquor Substances 0.000 description 2
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical class [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
239000012264 purified product Substances 0.000 description 2
238000000926 separation method Methods 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000005406 washing Methods 0.000 description 2
FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical class O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 1
WNLPNKDYWRKPQV-UHFFFAOYSA-N 1,3-diacetyl-4-benzyl-5-methylimidazol-2-one Chemical compound C(C)(=O)N1C(N(C(=C1CC1=CC=CC=C1)C)C(C)=O)=O WNLPNKDYWRKPQV-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
LCZRGWXVISWALK-UHFFFAOYSA-N 2-N-methyl-1-phenylpropane-1,2-diamine dihydrochloride Chemical compound CC(C(C1=CC=CC=C1)N)NC.Cl.Cl LCZRGWXVISWALK-UHFFFAOYSA-N 0.000 description 1
CXFFQOZYXJHZNJ-UHFFFAOYSA-N 3-phenylpropane-1,2-diamine Chemical compound NCC(N)CC1=CC=CC=C1 CXFFQOZYXJHZNJ-UHFFFAOYSA-N 0.000 description 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 description 1
GRKHTSOKVDBEHR-UHFFFAOYSA-N 4-(cyclohexylmethyl)-5-methylimidazolidin-2-one Chemical compound CC1NC(NC1CC1CCCCC1)=O GRKHTSOKVDBEHR-UHFFFAOYSA-N 0.000 description 1
PKMKZLLKQRSISH-UHFFFAOYSA-N 4-methyl-5-phenylimidazol-2-one Chemical compound CC1=NC(=O)N=C1C1=CC=CC=C1 PKMKZLLKQRSISH-UHFFFAOYSA-N 0.000 description 1
JMVQFRFKXOIRBI-UHFFFAOYSA-N 4-methylimidazol-2-one Chemical compound CC1=NC(=O)N=C1 JMVQFRFKXOIRBI-UHFFFAOYSA-N 0.000 description 1
PWYASFRWUIIFKM-UHFFFAOYSA-N CC(C(C(C=C1)=CC=C1OC(C)=O)N1C(C)=O)N(C(C)=O)C1=O Chemical compound CC(C(C(C=C1)=CC=C1OC(C)=O)N1C(C)=O)N(C(C)=O)C1=O PWYASFRWUIIFKM-UHFFFAOYSA-N 0.000 description 1
FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 1
QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
QDMDCALZVLUKJO-UHFFFAOYSA-N O=C1[NH+]=[C-]N=C1CC1=CC=CC=C1 Chemical compound O=C1[NH+]=[C-]N=C1CC1=CC=CC=C1 QDMDCALZVLUKJO-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
150000001555 benzenes Chemical group 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
238000005574 benzylation reaction Methods 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 description 1
230000006196 deacetylation Effects 0.000 description 1
238000003381 deacetylation reaction Methods 0.000 description 1
238000010586 diagram Methods 0.000 description 1
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
238000004821 distillation Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000004907 flux Effects 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000000295 fuel oil Substances 0.000 description 1
230000004927 fusion Effects 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
229940012189 methyl orange Drugs 0.000 description 1
231100000926 not very toxic Toxicity 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
150000003057 platinum Chemical class 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000002061 vacuum sublimation Methods 0.000 description 1