ES2226488T3 - Compuestos utiles en el tratamiento de enfermedades inflamatorias. - Google Patents

Info

Publication number

ES2226488T3

ES2226488T3 ES99964583T ES99964583T ES2226488T3 ES 2226488 T3 ES2226488 T3 ES 2226488T3 ES 99964583 T ES99964583 T ES 99964583T ES 99964583 T ES99964583 T ES 99964583T ES 2226488 T3 ES2226488 T3 ES 2226488T3

Authority

ES

Spain

Prior art keywords

amino

phenyl

oxy

acetyl

alkyl

Prior art date

1998-12-18

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Lifetime

Links

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 211
• 238000011282 treatment Methods 0.000 title claims description 17
• 208000027866 inflammatory disease Diseases 0.000 title description 3
• -1 nitro, hydroxy Chemical group 0.000 claims abstract description 188
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 89
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 62
• 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 17
• 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 15
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 12
• 150000002367 halogens Chemical class 0.000 claims abstract description 12
• 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 12
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 10
• 125000005843 halogen group Chemical group 0.000 claims abstract description 9
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 8
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 5
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims abstract description 5
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 3
• 125000002785 azepinyl group Chemical group 0.000 claims abstract description 3
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 3
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 3
• GVONPBONFIJAHJ-UHFFFAOYSA-N imidazolidin-4-one Chemical compound O=C1CNCN1 GVONPBONFIJAHJ-UHFFFAOYSA-N 0.000 claims abstract description 3
• 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 claims abstract description 3
• 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 claims abstract description 3
• 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 claims abstract description 3
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims abstract description 3
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims abstract description 3
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 117
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 89
• 239000011347 resin Substances 0.000 claims description 86
• 229920005989 resin Polymers 0.000 claims description 86
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 71
• 235000019260 propionic acid Nutrition 0.000 claims description 70
• 239000001257 hydrogen Substances 0.000 claims description 48
• 229910052739 hydrogen Inorganic materials 0.000 claims description 48
• DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 48
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 41
• 239000002253 acid Substances 0.000 claims description 31
• 238000000034 method Methods 0.000 claims description 31
• 150000003839 salts Chemical class 0.000 claims description 30
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 26
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 24
• TXCDCPKCNAJMEE-UHFFFAOYSA-N dibenzofuran Chemical group C1=CC=C2C3=CC=CC=C3OC2=C1 TXCDCPKCNAJMEE-UHFFFAOYSA-N 0.000 claims description 22
• 239000012453 solvate Substances 0.000 claims description 21
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 15
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
• 239000003795 chemical substances by application Substances 0.000 claims description 13
• 229910052760 oxygen Inorganic materials 0.000 claims description 11
• 238000002360 preparation method Methods 0.000 claims description 11
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 10
• UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 claims description 10
• 201000010099 disease Diseases 0.000 claims description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 8
• 125000003118 aryl group Chemical group 0.000 claims description 8
• 230000002757 inflammatory effect Effects 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 229910052717 sulfur Inorganic materials 0.000 claims description 8
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
• 238000010511 deprotection reaction Methods 0.000 claims description 6
• 150000002148 esters Chemical class 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 150000002431 hydrogen Chemical class 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 6
• 239000004793 Polystyrene Substances 0.000 claims description 5
• 229910052799 carbon Inorganic materials 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 229920002223 polystyrene Polymers 0.000 claims description 5
• UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 4
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 4
• 230000007062 hydrolysis Effects 0.000 claims description 4
• 238000006460 hydrolysis reaction Methods 0.000 claims description 4
• PPSXZSXHLIIACO-HEVIKAOCSA-N (2s)-2-[[(2s)-2-[[2-(2-tert-butylphenoxy)acetyl]amino]-4-methylpentanoyl]amino]-3-[4-[4-[(2-phenylacetyl)amino]piperidine-1-carbonyl]oxyphenyl]propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(OC(=O)N2CCC(CC2)NC(=O)CC=2C=CC=CC=2)=CC=1)C(O)=O)C(=O)COC1=CC=CC=C1C(C)(C)C PPSXZSXHLIIACO-HEVIKAOCSA-N 0.000 claims description 3
• FLJPNJMQUJHZIM-ZEQRLZLVSA-N (2s)-2-[[(2s)-4-methyl-2-[[2-(2-methylphenoxy)acetyl]amino]pentanoyl]amino]-3-[4-(morpholine-4-carbonyloxy)phenyl]propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(OC(=O)N2CCOCC2)=CC=1)C(O)=O)C(=O)COC1=CC=CC=C1C FLJPNJMQUJHZIM-ZEQRLZLVSA-N 0.000 claims description 3
• PGTAKIDUHHSBIG-NSOVKSMOSA-N (2s)-3-[4-(4-acetylpiperazine-1-carbonyl)oxyphenyl]-2-[[(2s)-2-[[2-(2-tert-butylphenoxy)acetyl]amino]-4-methylpentanoyl]amino]propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(OC(=O)N2CCN(CC2)C(C)=O)=CC=1)C(O)=O)C(=O)COC1=CC=CC=C1C(C)(C)C PGTAKIDUHHSBIG-NSOVKSMOSA-N 0.000 claims description 3
• YNDIBNHBFJYOFE-ACHIHNKUSA-N (2s)-3-[4-(4-benzoylpiperazine-1-carbonyl)oxyphenyl]-2-[[(2s)-2-[[2-(2-tert-butylphenoxy)acetyl]amino]-4-methylpentanoyl]amino]propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(OC(=O)N2CCN(CC2)C(=O)C=2C=CC=CC=2)=CC=1)C(O)=O)C(=O)COC1=CC=CC=C1C(C)(C)C YNDIBNHBFJYOFE-ACHIHNKUSA-N 0.000 claims description 3
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 3
• 150000001721 carbon Chemical group 0.000 claims description 3
• 150000001733 carboxylic acid esters Chemical class 0.000 claims description 3
• 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 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
• 229920005990 polystyrene resin Polymers 0.000 claims description 3
• 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• NKNFUWZGJLRHEF-SVBPBHIXSA-N (2s)-2-[[(2s)-2-(dibenzofuran-4-carbonylamino)-4-methylpentanoyl]amino]-3-[4-(morpholine-4-carbonyloxy)phenyl]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)C=1C=2OC3=CC=CC=C3C=2C=CC=1)CC(C)C)C(O)=O)C(C=C1)=CC=C1OC(=O)N1CCOCC1 NKNFUWZGJLRHEF-SVBPBHIXSA-N 0.000 claims description 2
• ODUJTJVQQFNWEX-PXLJZGITSA-N (2s)-2-[[(2s)-2-(dibenzofuran-4-carbonylamino)-4-methylpentanoyl]amino]-3-[4-[4-[(2-phenylacetyl)amino]piperidine-1-carbonyl]oxyphenyl]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)C=1C=2OC3=CC=CC=C3C=2C=CC=1)CC(C)C)C(O)=O)C(C=C1)=CC=C1OC(=O)N(CC1)CCC1NC(=O)CC1=CC=CC=C1 ODUJTJVQQFNWEX-PXLJZGITSA-N 0.000 claims description 2
• HUHLSTSVAXPHTF-VMPREFPWSA-N (2s)-2-[[(2s)-2-[[2-(1-bromonaphthalen-2-yl)oxyacetyl]amino]-4-methylpentanoyl]amino]-3-[4-[4-(furan-2-carbonyl)piperazine-1-carbonyl]oxyphenyl]propanoic acid Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)COC=1C(=C2C=CC=CC2=CC=1)Br)CC(C)C)C(O)=O)C(C=C1)=CC=C1OC(=O)N(CC1)CCN1C(=O)C1=CC=CO1 HUHLSTSVAXPHTF-VMPREFPWSA-N 0.000 claims description 2
• SBCVXKWLVINGKC-ZEQRLZLVSA-N (2s)-2-[[(2s)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-3-[4-(morpholine-4-carbonyloxy)phenyl]propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(OC(=O)N2CCOCC2)=CC=1)C(O)=O)C(=O)OCC1=CC=CC=C1 SBCVXKWLVINGKC-ZEQRLZLVSA-N 0.000 claims description 2
• VVZPENFOQVEKIV-VMPREFPWSA-N (2s)-2-[[(2s)-4-methyl-2-[[2-[4-(piperidine-1-carbonyl)phenoxy]acetyl]amino]pentanoyl]amino]-3-[4-(morpholine-4-carbonyloxy)phenyl]propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(OC(=O)N2CCOCC2)=CC=1)C(O)=O)C(=O)COC(C=C1)=CC=C1C(=O)N1CCCCC1 VVZPENFOQVEKIV-VMPREFPWSA-N 0.000 claims description 2
• JPJAYGCKRULCOQ-UIOOFZCWSA-N (2s)-3-[4-(4-acetylpiperazine-1-carbonyl)oxyphenyl]-2-[[(2s)-4-methyl-2-[[2-(2-methylphenoxy)acetyl]amino]pentanoyl]amino]propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(OC(=O)N2CCN(CC2)C(C)=O)=CC=1)C(O)=O)C(=O)COC1=CC=CC=C1C JPJAYGCKRULCOQ-UIOOFZCWSA-N 0.000 claims description 2
• BTPNIOFQMCTNHX-KYJUHHDHSA-N (2s)-3-[4-(4-carbamoylpiperidine-1-carbonyl)oxyphenyl]-2-[[(2s)-4-methyl-2-[[2-[4-(piperidine-1-carbonyl)phenoxy]acetyl]amino]pentanoyl]amino]propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(OC(=O)N2CCC(CC2)C(N)=O)=CC=1)C(O)=O)C(=O)COC(C=C1)=CC=C1C(=O)N1CCCCC1 BTPNIOFQMCTNHX-KYJUHHDHSA-N 0.000 claims description 2
• LWTXVGKEFCWSEV-UIOOFZCWSA-N (2s)-3-[4-[4-(furan-2-carbonyl)piperazine-1-carbonyl]oxyphenyl]-2-[[(2s)-2-[[2-(2-iodophenoxy)acetyl]amino]-4-methylpentanoyl]amino]propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(OC(=O)N2CCN(CC2)C(=O)C=2OC=CC=2)=CC=1)C(O)=O)C(=O)COC1=CC=CC=C1I LWTXVGKEFCWSEV-UIOOFZCWSA-N 0.000 claims description 2
• KMSVUEKDRPJQNE-BCRBLDSWSA-N (2s)-3-[4-[4-[(2-cyclohexylacetyl)amino]piperidine-1-carbonyl]oxyphenyl]-2-[[(2s)-2-[[2-(2-cyclohexylphenoxy)acetyl]amino]-4-methylpentanoyl]amino]propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(OC(=O)N2CCC(CC2)NC(=O)CC2CCCCC2)=CC=1)C(O)=O)C(=O)COC1=CC=CC=C1C1CCCCC1 KMSVUEKDRPJQNE-BCRBLDSWSA-N 0.000 claims description 2
• AZUVFLGTAWFMHP-CONSDPRKSA-N (2s)-3-[4-[4-[(2-cyclohexylacetyl)amino]piperidine-1-carbonyl]oxyphenyl]-2-[[(2s)-2-[[2-(2-iodophenoxy)acetyl]amino]-4-methylpentanoyl]amino]propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(OC(=O)N2CCC(CC2)NC(=O)CC2CCCCC2)=CC=1)C(O)=O)C(=O)COC1=CC=CC=C1I AZUVFLGTAWFMHP-CONSDPRKSA-N 0.000 claims description 2
• 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 2
• OXRSFHYBIRFJSF-UHFFFAOYSA-N 3-phenyl-1,4-dihydropyrazol-5-one Chemical compound N1C(=O)CC(C=2C=CC=CC=2)=N1 OXRSFHYBIRFJSF-UHFFFAOYSA-N 0.000 claims description 2
• ORSUMIZRRGPJBR-UHFFFAOYSA-N 4,5-dihydro-1h-pyridazin-6-one Chemical compound O=C1CCC=NN1 ORSUMIZRRGPJBR-UHFFFAOYSA-N 0.000 claims description 2
• 101100118680 Caenorhabditis elegans sec-61.G gene Proteins 0.000 claims description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 5
• MNASXWZLHZIIKC-BCRBLDSWSA-N (2s)-2-[[(2s)-2-[[2-(2-benzoylphenoxy)acetyl]amino]-4-methylpentanoyl]amino]-3-[4-[4-[(2-phenylacetyl)amino]piperidine-1-carbonyl]oxyphenyl]propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(OC(=O)N2CCC(CC2)NC(=O)CC=2C=CC=CC=2)=CC=1)C(O)=O)C(=O)COC1=CC=CC=C1C(=O)C1=CC=CC=C1 MNASXWZLHZIIKC-BCRBLDSWSA-N 0.000 claims 1
• RZMCXMNNXGCFQG-DQEYMECFSA-N (2s)-3-[4-(4-carbamoylpiperidine-1-carbonyl)oxyphenyl]-2-[[(2s)-4-methyl-2-[[2-(2-methylphenoxy)acetyl]amino]pentanoyl]amino]propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(OC(=O)N2CCC(CC2)C(N)=O)=CC=1)C(O)=O)C(=O)COC1=CC=CC=C1C RZMCXMNNXGCFQG-DQEYMECFSA-N 0.000 claims 1
• SHNAAOJNYHBXJK-BCRBLDSWSA-N (2s)-3-[4-[4-[[2-(4-chlorophenyl)acetyl]amino]piperidine-1-carbonyl]oxyphenyl]-2-[[(2s)-2-[[2-(2-cyclohexylphenoxy)acetyl]amino]-4-methylpentanoyl]amino]propanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(OC(=O)N2CCC(CC2)NC(=O)CC=2C=CC(Cl)=CC=2)=CC=1)C(O)=O)C(=O)COC1=CC=CC=C1C1CCCCC1 SHNAAOJNYHBXJK-BCRBLDSWSA-N 0.000 claims 1
• 230000001800 adrenalinergic effect Effects 0.000 claims 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
• XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 1
• 239000000018 receptor agonist Substances 0.000 claims 1
• 229940044601 receptor agonist Drugs 0.000 claims 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 8
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 460
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 297
• 239000000543 intermediate Substances 0.000 description 210
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 179
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 153
• 239000000243 solution Substances 0.000 description 141
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 130
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 129
• 239000000203 mixture Substances 0.000 description 122
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 113
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 110
• 238000003756 stirring Methods 0.000 description 104
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 103
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 101
• 239000007787 solid Substances 0.000 description 101
• 239000010410 layer Substances 0.000 description 93
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 91
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 83
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 73
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 72
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 68
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 63
• 239000012299 nitrogen atmosphere Substances 0.000 description 59
• 239000000741 silica gel Substances 0.000 description 59
• 229910002027 silica gel Inorganic materials 0.000 description 59
• 238000003818 flash chromatography Methods 0.000 description 57
• 239000012043 crude product Substances 0.000 description 52
• 229920006395 saturated elastomer Polymers 0.000 description 44
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
• 239000006260 foam Substances 0.000 description 42
• 239000000284 extract Substances 0.000 description 41
• 235000017557 sodium bicarbonate Nutrition 0.000 description 41
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 41
• 239000002904 solvent Substances 0.000 description 39
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 38
• 229910052938 sodium sulfate Inorganic materials 0.000 description 38
• 235000011152 sodium sulphate Nutrition 0.000 description 38
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 36
• 235000019441 ethanol Nutrition 0.000 description 34
• 239000012267 brine Substances 0.000 description 33
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 32
• 235000019341 magnesium sulphate Nutrition 0.000 description 32
• 239000000706 filtrate Substances 0.000 description 28
• 239000000725 suspension Substances 0.000 description 28
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 27
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 26
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 25
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