CA2480106A1 - Morpholinyl-urea derivatives for use of the treatment of inflammatory diseases - Google Patents

Info

Publication number

CA2480106A1

CA2480106A1 CA002480106A CA2480106A CA2480106A1 CA 2480106 A1 CA2480106 A1 CA 2480106A1 CA 002480106 A CA002480106 A CA 002480106A CA 2480106 A CA2480106 A CA 2480106A CA 2480106 A1 CA2480106 A1 CA 2480106A1

Authority

CA

Canada

Prior art keywords

methyl

formula

compound

morpholin

oxadiazol

Prior art date

2002-03-28

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 238000011282 treatment Methods 0.000 title claims description 15
• 208000027866 inflammatory disease Diseases 0.000 title description 6
• XMVNCHHPCRFUFT-UHFFFAOYSA-N morpholin-4-ylurea Chemical class NC(=O)NN1CCOCC1 XMVNCHHPCRFUFT-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 307
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 54
• 239000001257 hydrogen Substances 0.000 claims abstract description 52
• 150000003839 salts Chemical class 0.000 claims abstract description 43
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 41
• 239000012453 solvate Substances 0.000 claims abstract description 34
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 26
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 21
• 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 5
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 7
• -1 5-methylisoxazol-3--yl Chemical group 0.000 claims description 411
• 238000006243 chemical reaction Methods 0.000 claims description 51
• 238000000034 method Methods 0.000 claims description 50
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 30
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 22
• 239000004202 carbamide Substances 0.000 claims description 19
• 208000006673 asthma Diseases 0.000 claims description 17
• 238000002360 preparation method Methods 0.000 claims description 15
• 230000008569 process Effects 0.000 claims description 15
• 125000001544 thienyl group Chemical group 0.000 claims description 15
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 12
• 125000001153 fluoro group Chemical group F* 0.000 claims description 11
• 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 claims description 10
• 125000006239 protecting group Chemical group 0.000 claims description 10
• 206010039083 rhinitis Diseases 0.000 claims description 8
• 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 claims description 7
• 239000003814 drug Substances 0.000 claims description 7
• 230000004968 inflammatory condition Effects 0.000 claims description 7
• 229920005989 resin Polymers 0.000 claims description 7
• 239000011347 resin Substances 0.000 claims description 7
• HIMWHLGWENNHOO-RUINGEJQSA-N (4-nitrophenyl) n-[[(2s)-4-[1-(3,4-difluorophenyl)ethyl]morpholin-2-yl]methyl]carbamate Chemical compound C([C@@H]1OCCN(C1)C(C)C=1C=C(F)C(F)=CC=1)NC(=O)OC1=CC=C([N+]([O-])=O)C=C1 HIMWHLGWENNHOO-RUINGEJQSA-N 0.000 claims description 6
• 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 229920005990 polystyrene resin Polymers 0.000 claims description 6
• 150000002431 hydrogen Chemical group 0.000 claims description 5
• 229940124597 therapeutic agent Drugs 0.000 claims description 5
• 125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 claims description 4
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 4
• CHFLRXHBQCODJY-ZDUSSCGKSA-N 1-[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-(1,3-thiazol-2-ylmethyl)urea Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1C[C@H](CNC(=O)NCC=2SC=CN=2)OCC1 CHFLRXHBQCODJY-ZDUSSCGKSA-N 0.000 claims description 3
• SOANXCFVMUFQHE-AWEZNQCLSA-N 1-[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-[(4-methyl-1,3-thiazol-2-yl)methyl]urea Chemical compound CC1=CSC(CNC(=O)NC[C@@H]2OCCN(CC=3C=C(Cl)C(Cl)=CC=3)C2)=N1 SOANXCFVMUFQHE-AWEZNQCLSA-N 0.000 claims description 3
• KMAFRTKBDGSAJJ-IBGZPJMESA-N 1-[[3-(4-chlorophenyl)-1,2-oxazol-5-yl]methyl]-3-[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]urea Chemical compound C1=CC(Cl)=CC=C1C1=NOC(CNC(=O)NC[C@@H]2OCCN(CC=3C=C(Cl)C(Cl)=CC=3)C2)=C1 KMAFRTKBDGSAJJ-IBGZPJMESA-N 0.000 claims description 3
• CHFLRXHBQCODJY-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-(1,3-thiazol-2-ylmethyl)urea Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1CC(CNC(=O)NCC=2SC=CN=2)OCC1 CHFLRXHBQCODJY-UHFFFAOYSA-N 0.000 claims description 3
• LJQCWQGMVJGSKQ-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-(1h-indol-4-ylmethyl)urea Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1CC(CNC(=O)NCC=2C=3C=CNC=3C=CC=2)OCC1 LJQCWQGMVJGSKQ-UHFFFAOYSA-N 0.000 claims description 3
• YSSDLSCDXACWQT-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-(1h-indol-5-ylmethyl)urea Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1CC(CNC(=O)NCC=2C=C3C=CNC3=CC=2)OCC1 YSSDLSCDXACWQT-UHFFFAOYSA-N 0.000 claims description 3
• YESMWHHSKLCUDO-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-(2-thiophen-2-ylethyl)urea Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1CC(CNC(=O)NCCC=2SC=CC=2)OCC1 YESMWHHSKLCUDO-UHFFFAOYSA-N 0.000 claims description 3
• UBRNPKULFLNKTN-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-(furan-2-ylmethyl)urea Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1CC(CNC(=O)NCC=2OC=CC=2)OCC1 UBRNPKULFLNKTN-UHFFFAOYSA-N 0.000 claims description 3
• JOAMKEZJIZMCCP-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-(pyridin-3-ylmethyl)urea Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1CC(CNC(=O)NCC=2C=NC=CC=2)OCC1 JOAMKEZJIZMCCP-UHFFFAOYSA-N 0.000 claims description 3
• PMMVLXWWCMYNLR-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-(thiophen-2-ylmethyl)urea Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1CC(CNC(=O)NCC=2SC=CC=2)OCC1 PMMVLXWWCMYNLR-UHFFFAOYSA-N 0.000 claims description 3
• ZXAYMAJLQPFCEI-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-[(2-methyl-1,3-thiazol-4-yl)methyl]urea Chemical compound S1C(C)=NC(CNC(=O)NCC2OCCN(CC=3C=C(Cl)C(Cl)=CC=3)C2)=C1 ZXAYMAJLQPFCEI-UHFFFAOYSA-N 0.000 claims description 3
• ZALONBKTWCFUDD-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-[(3-methoxy-1,2-thiazol-5-yl)methyl]urea Chemical compound S1N=C(OC)C=C1CNC(=O)NCC1OCCN(CC=2C=C(Cl)C(Cl)=CC=2)C1 ZALONBKTWCFUDD-UHFFFAOYSA-N 0.000 claims description 3
• PONVDQFSFUCTIN-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-[(6-methoxypyridin-3-yl)methyl]urea Chemical compound C1=NC(OC)=CC=C1CNC(=O)NCC1OCCN(CC=2C=C(Cl)C(Cl)=CC=2)C1 PONVDQFSFUCTIN-UHFFFAOYSA-N 0.000 claims description 3
• NYLJYXFMJQIKII-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-[[5-[(dimethylamino)methyl]thiophen-2-yl]methyl]urea Chemical compound S1C(CN(C)C)=CC=C1CNC(=O)NCC1OCCN(CC=2C=C(Cl)C(Cl)=CC=2)C1 NYLJYXFMJQIKII-UHFFFAOYSA-N 0.000 claims description 3
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
• FWJJBJSRDWAPHW-UHFFFAOYSA-N 5-(aminomethyl)-n-methylfuran-3-carboxamide Chemical compound CNC(=O)C1=COC(CN)=C1 FWJJBJSRDWAPHW-UHFFFAOYSA-N 0.000 claims description 3
• FLDBJBTUVYXSJV-UHFFFAOYSA-N 5-(aminomethyl)-n-methylthiophene-3-carboxamide Chemical compound CNC(=O)C1=CSC(CN)=C1 FLDBJBTUVYXSJV-UHFFFAOYSA-N 0.000 claims description 3
• QOYKPLLIAVKPQG-UHFFFAOYSA-N 5-[[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methylcarbamoylamino]methyl]pyridine-3-carboxamide Chemical compound NC(=O)C1=CN=CC(CNC(=O)NCC2OCCN(CC=3C=C(Cl)C(Cl)=CC=3)C2)=C1 QOYKPLLIAVKPQG-UHFFFAOYSA-N 0.000 claims description 3
• 239000000969 carrier Substances 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• FSKWRNINWRUSHD-UHFFFAOYSA-N methyl 2-(aminomethyl)-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1=COC(CN)=N1 FSKWRNINWRUSHD-UHFFFAOYSA-N 0.000 claims description 3
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 3
• 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 claims description 3
• DJVBYKUXZPCRCL-INIZCTEOSA-N (4-nitrophenyl) n-[[(2s)-4-[(3-chloro-4-fluorophenyl)methyl]morpholin-2-yl]methyl]carbamate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC(=O)NC[C@@H]1OCCN(CC=2C=C(Cl)C(F)=CC=2)C1 DJVBYKUXZPCRCL-INIZCTEOSA-N 0.000 claims description 2
• XLUKYSBCGPFVOU-UHFFFAOYSA-N 1-[(5-amino-1-phenylpyrazol-4-yl)methyl]-3-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]urea Chemical compound C1=NN(C=2C=CC=CC=2)C(N)=C1CNC(=O)NCC(OCC1)CN1CC1=CC=C(Cl)C(Cl)=C1 XLUKYSBCGPFVOU-UHFFFAOYSA-N 0.000 claims description 2
• JZBGNRGEOVQVEE-LBPRGKRZSA-N 1-[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-[(2-methyltetrazol-5-yl)methyl]urea Chemical compound CN1N=NC(CNC(=O)NC[C@@H]2OCCN(CC=3C=C(Cl)C(Cl)=CC=3)C2)=N1 JZBGNRGEOVQVEE-LBPRGKRZSA-N 0.000 claims description 2
• JLJGCRRYIYNEQJ-FQEVSTJZSA-N 1-[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-[[3-(4-methoxyphenyl)-1,2-oxazol-5-yl]methyl]urea Chemical compound C1=CC(OC)=CC=C1C1=NOC(CNC(=O)NC[C@@H]2OCCN(CC=3C=C(Cl)C(Cl)=CC=3)C2)=C1 JLJGCRRYIYNEQJ-FQEVSTJZSA-N 0.000 claims description 2
• CBYLTQKFXCIQCV-HNNXBMFYSA-N 1-[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-[[4-(hydrazinecarbonyl)furan-2-yl]methyl]urea Chemical compound NNC(=O)C1=COC(CNC(=O)NC[C@@H]2OCCN(CC=3C=C(Cl)C(Cl)=CC=3)C2)=C1 CBYLTQKFXCIQCV-HNNXBMFYSA-N 0.000 claims description 2
• JZBGNRGEOVQVEE-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-[(2-methyltetrazol-5-yl)methyl]urea Chemical compound CN1N=NC(CNC(=O)NCC2OCCN(CC=3C=C(Cl)C(Cl)=CC=3)C2)=N1 JZBGNRGEOVQVEE-UHFFFAOYSA-N 0.000 claims description 2
• WQNPBIUZGHSLPX-UHFFFAOYSA-N 1-[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]-3-[[5-[(dimethylamino)methyl]furan-2-yl]methyl]urea Chemical compound O1C(CN(C)C)=CC=C1CNC(=O)NCC1OCCN(CC=2C=C(Cl)C(Cl)=CC=2)C1 WQNPBIUZGHSLPX-UHFFFAOYSA-N 0.000 claims description 2
• JFLBVUOVXQIGRP-LBPRGKRZSA-N 1-[[5-(chloromethyl)-1,3,4-oxadiazol-2-yl]methyl]-3-[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methyl]urea Chemical compound O1C(CCl)=NN=C1CNC(=O)NC[C@@H]1OCCN(CC=2C=C(Cl)C(Cl)=CC=2)C1 JFLBVUOVXQIGRP-LBPRGKRZSA-N 0.000 claims description 2
• GUQLIIDOUGKDRN-UHFFFAOYSA-N 2-(5-methyl-1,3,4-oxadiazol-2-yl)ethanamine;hydrochloride Chemical compound Cl.CC1=NN=C(CCN)O1 GUQLIIDOUGKDRN-UHFFFAOYSA-N 0.000 claims description 2
• 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 2
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
• HBAHZZVIEFRTEY-UHFFFAOYSA-N 2-heptylcyclohex-2-en-1-one Chemical compound CCCCCCCC1=CCCCC1=O HBAHZZVIEFRTEY-UHFFFAOYSA-N 0.000 claims description 2
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
• SHWHZSUZZGMZID-UHFFFAOYSA-N 5-(aminomethyl)-n-methyl-1,3,4-oxadiazole-2-carboxamide;hydrochloride Chemical compound Cl.CNC(=O)C1=NN=C(CN)O1 SHWHZSUZZGMZID-UHFFFAOYSA-N 0.000 claims description 2
• 229920001367 Merrifield resin Polymers 0.000 claims description 2
• 241001465754 Metazoa Species 0.000 claims description 2
• 125000004532 benzofuran-3-yl group Chemical group O1C=C(C2=C1C=CC=C2)* 0.000 claims description 2
• 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 2
• 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 2
• CRMHHVVQZYELMA-UHFFFAOYSA-N methyl 2-[[[4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methylcarbamoylamino]methyl]-4-methyl-1,3-thiazole-5-carboxylate Chemical compound CC1=C(C(=O)OC)SC(CNC(=O)NCC2OCCN(CC=3C=C(Cl)C(Cl)=CC=3)C2)=N1 CRMHHVVQZYELMA-UHFFFAOYSA-N 0.000 claims description 2
• GACCYZRDGNSLGQ-INIZCTEOSA-N n-[[5-[[[(2s)-4-[(3,4-dichlorophenyl)methyl]morpholin-2-yl]methylcarbamoylamino]methyl]furan-3-carbonyl]amino]formamide Chemical compound C1=C(Cl)C(Cl)=CC=C1CN1C[C@H](CNC(=O)NCC=2OC=C(C=2)C(=O)NNC=O)OCC1 GACCYZRDGNSLGQ-INIZCTEOSA-N 0.000 claims description 2
• BNCNNWWRGRSEDP-UHFFFAOYSA-N n-methyl-5-[[(2,2,2-trifluoroacetyl)amino]methyl]furan-3-carboxamide Chemical compound CNC(=O)C1=COC(CNC(=O)C(F)(F)F)=C1 BNCNNWWRGRSEDP-UHFFFAOYSA-N 0.000 claims description 2
• RSHUXWPDNREGKV-UHFFFAOYSA-N n-methyl-5-[[(2,2,2-trifluoroacetyl)amino]methyl]thiophene-3-carboxamide Chemical compound CNC(=O)C1=CSC(CNC(=O)C(F)(F)F)=C1 RSHUXWPDNREGKV-UHFFFAOYSA-N 0.000 claims description 2
• XYHFNWLMOULUAT-ZDUSSCGKSA-N tert-butyl n-[[(2s)-4-[(3-chloro-4-fluorophenyl)methyl]morpholin-2-yl]methyl]carbamate Chemical compound C1CO[C@@H](CNC(=O)OC(C)(C)C)CN1CC1=CC=C(F)C(Cl)=C1 XYHFNWLMOULUAT-ZDUSSCGKSA-N 0.000 claims description 2
• HWTMFHDEXRMMSD-PYMCNQPYSA-N tert-butyl n-[[(2s)-4-[1-(3,4-difluorophenyl)ethyl]morpholin-2-yl]methyl]carbamate Chemical compound C=1C=C(F)C(F)=CC=1C(C)N1CCO[C@@H](CNC(=O)OC(C)(C)C)C1 HWTMFHDEXRMMSD-PYMCNQPYSA-N 0.000 claims description 2
• PMWQINVTMXVGNI-UHFFFAOYSA-N tert-butyl n-[[5-(methylcarbamoyl)-1,3,4-oxadiazol-2-yl]methyl]carbamate Chemical compound CNC(=O)C1=NN=C(CNC(=O)OC(C)(C)C)O1 PMWQINVTMXVGNI-UHFFFAOYSA-N 0.000 claims description 2
• WVOJCKHURCFFLB-UHFFFAOYSA-N C(C)(=O)NNC(CCNC(O)=O)=O Chemical compound C(C)(=O)NNC(CCNC(O)=O)=O WVOJCKHURCFFLB-UHFFFAOYSA-N 0.000 claims 1
• NSSUDNICEDDZMG-UHFFFAOYSA-N CC1=NN=C(O1)CCNC(O)=O Chemical compound CC1=NN=C(O1)CCNC(O)=O NSSUDNICEDDZMG-UHFFFAOYSA-N 0.000 claims 1
• 102100024167 C-C chemokine receptor type 3 Human genes 0.000 abstract description 19
• 101710149862 C-C chemokine receptor type 3 Proteins 0.000 abstract description 19
• 239000005557 antagonist Substances 0.000 abstract description 7
• 238000002560 therapeutic procedure Methods 0.000 abstract description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 323
• 239000000243 solution Substances 0.000 description 109
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 102
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
• 239000000203 mixture Substances 0.000 description 93
• 239000002904 solvent Substances 0.000 description 78
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 62
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 62
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 59
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 58
• 125000001424 substituent group Chemical group 0.000 description 46
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 44
• 125000000217 alkyl group Chemical group 0.000 description 39
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 37
• 239000007787 solid Substances 0.000 description 35
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
• 239000000725 suspension Substances 0.000 description 34
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
• 239000002585 base Substances 0.000 description 28
• 229910052757 nitrogen Inorganic materials 0.000 description 28
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
• 229910021529 ammonia Inorganic materials 0.000 description 25
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
• 238000010992 reflux Methods 0.000 description 24
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 23
• 238000005342 ion exchange Methods 0.000 description 22
• 239000003921 oil Substances 0.000 description 21
• 235000019198 oils Nutrition 0.000 description 21
• 235000019441 ethanol Nutrition 0.000 description 20
• 125000005843 halogen group Chemical group 0.000 description 20
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
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