DE60213609T2 - THIENOi2,3-döPYRIMIDINEDIONES ALS INHIBITOREN VON T-ZELLEN-PROLIFERATION - Google Patents

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Publication number

DE60213609T2

DE60213609T2 DE60213609T DE60213609T DE60213609T2 DE 60213609 T2 DE60213609 T2 DE 60213609T2 DE 60213609 T DE60213609 T DE 60213609T DE 60213609 T DE60213609 T DE 60213609T DE 60213609 T2 DE60213609 T2 DE 60213609T2

Authority

DE

Germany

Prior art keywords

methyl

pyrimidine

methoxy

tetrahydro

dimethyl

Prior art date

2001-07-19

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 - Fee Related

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• 230000006052 T cell proliferation Effects 0.000 title 1
• 239000003112 inhibitor Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 269
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 105
• 238000000034 method Methods 0.000 claims abstract description 100
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 88
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 79
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 46
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 30
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 30
• 125000001424 substituent group Chemical group 0.000 claims abstract description 29
• 125000003118 aryl group Chemical group 0.000 claims abstract description 28
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 24
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 23
• 239000001301 oxygen Chemical group 0.000 claims abstract description 23
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 14
• 125000004122 cyclic group Chemical group 0.000 claims abstract description 13
• 125000006413 ring segment Chemical group 0.000 claims abstract description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 5
• -1 hydroxy, amino Chemical group 0.000 claims description 285
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 67
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 56
• 150000003839 salts Chemical class 0.000 claims description 47
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 35
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
• 125000000623 heterocyclic group Chemical group 0.000 claims description 26
• 229910052736 halogen Inorganic materials 0.000 claims description 25
• 125000004043 oxo group Chemical group O=* 0.000 claims description 25
• 150000002367 halogens Chemical class 0.000 claims description 24
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 23
• 238000006243 chemical reaction Methods 0.000 claims description 22
• 229910052717 sulfur Inorganic materials 0.000 claims description 21
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 19
• 239000001257 hydrogen Substances 0.000 claims description 19
• 229910052739 hydrogen Inorganic materials 0.000 claims description 19
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 17
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
• 125000004385 trihaloalkyl group Chemical group 0.000 claims description 15
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 13
• 125000004982 dihaloalkyl group Chemical group 0.000 claims description 13
• 125000001188 haloalkyl group Chemical group 0.000 claims description 13
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
• 125000004414 alkyl thio group Chemical group 0.000 claims description 12
• 239000011593 sulfur Chemical group 0.000 claims description 12
• 125000000464 thioxo group Chemical group S=* 0.000 claims description 12
• 125000003545 alkoxy group Chemical group 0.000 claims description 11
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 11
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 11
• 125000002883 imidazolyl group Chemical group 0.000 claims description 11
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 11
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
• 125000005493 quinolyl group Chemical group 0.000 claims description 10
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 9
• 125000001041 indolyl group Chemical group 0.000 claims description 9
• 230000035755 proliferation Effects 0.000 claims description 9
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 8
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 8
• 125000003342 alkenyl group Chemical group 0.000 claims description 8
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 8
• 125000005843 halogen group Chemical group 0.000 claims description 8
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
• GXAYTGQJFGCPQE-UHFFFAOYSA-N 1-ethyl-n-methoxy-n,3-dimethyl-2,4-dioxo-6-(quinolin-4-ylmethyl)thieno[2,3-d]pyrimidine-5-carboxamide Chemical compound C1=CC=C2C(CC=3SC=4N(C(N(C)C(=O)C=4C=3C(=O)N(C)OC)=O)CC)=CC=NC2=C1 GXAYTGQJFGCPQE-UHFFFAOYSA-N 0.000 claims description 7
• 125000000524 functional group Chemical group 0.000 claims description 7
• 125000005946 imidazo[1,2-a]pyridyl group Chemical group 0.000 claims description 7
• 238000002360 preparation method Methods 0.000 claims description 7
• 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 6
• 210000001744 T-lymphocyte Anatomy 0.000 claims description 6
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
• NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims description 5
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
• TYONQVMMGHFCBR-UHFFFAOYSA-N 1-(cyclopropylmethyl)-n-methoxy-n,3-dimethyl-2,4-dioxo-6-(quinolin-4-ylmethyl)thieno[2,3-d]pyrimidine-5-carboxamide Chemical compound O=C1N(C)C(=O)C=2C(C(=O)N(C)OC)=C(CC=3C4=CC=CC=C4N=CC=3)SC=2N1CC1CC1 TYONQVMMGHFCBR-UHFFFAOYSA-N 0.000 claims description 5
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 5
• PXROSKUMGPMFKF-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-2,4-dioxo-1-propyl-6-(quinolin-4-ylmethyl)thieno[2,3-d]pyrimidine-5-carboxamide Chemical compound C1=CC=C2C(CC=3SC=4N(C(N(C)C(=O)C=4C=3C(=O)N(C)OC)=O)CCC)=CC=NC2=C1 PXROSKUMGPMFKF-UHFFFAOYSA-N 0.000 claims description 5
• BZGPCILIRUKTSL-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-6-[(2-methyl-1h-indol-3-yl)methyl]-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CC=C3NC=1C)=C2C(=O)N(C)OC BZGPCILIRUKTSL-UHFFFAOYSA-N 0.000 claims description 5
• 230000008569 process Effects 0.000 claims description 5
• 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims description 5
• 238000002560 therapeutic procedure Methods 0.000 claims description 5
• JWJLXCMYIXOEKN-UHFFFAOYSA-N 6-(2h-indazol-3-ylmethyl)-n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CC=C3NN=1)=C2C(=O)N(C)OC JWJLXCMYIXOEKN-UHFFFAOYSA-N 0.000 claims description 4
• SLMBPMJXKUQBMS-UHFFFAOYSA-N 6-[(1-acetylindol-3-yl)methyl]-n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CC=C3N(C(C)=O)C=1)=C2C(=O)N(C)OC SLMBPMJXKUQBMS-UHFFFAOYSA-N 0.000 claims description 4
• CBYGQTUGONAURO-UHFFFAOYSA-N 6-[(2-chloroimidazol-1-yl)methyl]-n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound S1C=2N(CC(C)C)C(=O)N(C)C(=O)C=2C(C(=O)N(C)OC)=C1CN1C=CN=C1Cl CBYGQTUGONAURO-UHFFFAOYSA-N 0.000 claims description 4
• LQRASRFLUDKWAX-UHFFFAOYSA-N 6-[(4,5-dichloro-2-methylimidazol-1-yl)methyl]-n-methoxy-n,3-dimethyl-2,4-dioxo-1-propan-2-ylthieno[2,3-d]pyrimidine-5-carboxamide Chemical compound S1C=2N(C(C)C)C(=O)N(C)C(=O)C=2C(C(=O)N(C)OC)=C1CN1C(C)=NC(Cl)=C1Cl LQRASRFLUDKWAX-UHFFFAOYSA-N 0.000 claims description 4
• YIYNBXNJBFLKQE-UHFFFAOYSA-N 6-[(4,5-dichloro-2-methylimidazol-1-yl)methyl]-n-methoxy-n,3-dimethyl-2,4-dioxo-1-propylthieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CON(C)C(=O)C=1C=2C(=O)N(C)C(=O)N(CCC)C=2SC=1CN1C(C)=NC(Cl)=C1Cl YIYNBXNJBFLKQE-UHFFFAOYSA-N 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 4
• HWQFWHOXXCWOJM-UHFFFAOYSA-N n-(2-hydroxyethyl)-n-methoxy-3-methyl-1-(2-methylpropyl)-6-[(2-methylsulfanylimidazol-1-yl)methyl]-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound S1C=2N(CC(C)C)C(=O)N(C)C(=O)C=2C(C(=O)N(CCO)OC)=C1CN1C=CN=C1SC HWQFWHOXXCWOJM-UHFFFAOYSA-N 0.000 claims description 4
• FQXRBDBNEITFPH-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-[(2-oxo-1,3-benzothiazol-3-yl)methyl]thieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CN1C(SC3=CC=CC=C31)=O)=C2C(=O)N(C)OC FQXRBDBNEITFPH-UHFFFAOYSA-N 0.000 claims description 4
• GJWOKVFESRKLOA-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-[(2-oxo-1,3-benzoxazol-3-yl)methyl]thieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CN1C(OC3=CC=CC=C31)=O)=C2C(=O)N(C)OC GJWOKVFESRKLOA-UHFFFAOYSA-N 0.000 claims description 4
• GQLKYTHLQYPEBI-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-6-[(2-methylsulfanylimidazol-1-yl)methyl]-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound S1C=2N(CC(C)C)C(=O)N(C)C(=O)C=2C(C(=O)N(C)OC)=C1CN1C=CN=C1SC GQLKYTHLQYPEBI-UHFFFAOYSA-N 0.000 claims description 4
• CPMMQUAFPDUCCF-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-6-[(2-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-2,4-dioxo-1-propylthieno[2,3-d]pyrimidine-5-carboxamide Chemical compound C1=CC=C2C(CC=3SC=4N(C(N(C)C(=O)C=4C=3C(=O)N(C)OC)=O)CCC)=C(C)NC2=N1 CPMMQUAFPDUCCF-UHFFFAOYSA-N 0.000 claims description 4
• QXICFGCADMCHQD-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-6-[[2-(methylamino)benzimidazol-1-yl]methyl]-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CN1C3=CC=CC=C3N=C1NC)=C2C(=O)N(C)OC QXICFGCADMCHQD-UHFFFAOYSA-N 0.000 claims description 4
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
• 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 3
• KKZUMAMOMRDVKA-UHFFFAOYSA-N 2-chloropropane Chemical group [CH2]C(C)Cl KKZUMAMOMRDVKA-UHFFFAOYSA-N 0.000 claims description 3
• LBBGSBPIRZEZSY-UHFFFAOYSA-N 6-(1h-indol-3-ylmethyl)-n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CC=C3NC=1)=C2C(=O)N(C)OC LBBGSBPIRZEZSY-UHFFFAOYSA-N 0.000 claims description 3
• SFXOTKPNEUNUFM-UHFFFAOYSA-N 6-(1h-indole-3-carbonyl)-n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound C1=CC=C2C(C(=O)C3=C(C=4C(=O)N(C)C(=O)N(CC(C)C)C=4S3)C(=O)N(C)OC)=CNC2=C1 SFXOTKPNEUNUFM-UHFFFAOYSA-N 0.000 claims description 3
• YHKNTGMCONSUEO-UHFFFAOYSA-N 6-[(4,5-dichloro-2-methylimidazol-1-yl)methyl]-n-(2-hydroxyethoxy)-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound OCCON(C)C(=O)C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CN1C(C)=NC(Cl)=C1Cl YHKNTGMCONSUEO-UHFFFAOYSA-N 0.000 claims description 3
• COWXFPKRNKUORL-UHFFFAOYSA-N 6-[(4,5-dichloro-2-methylimidazol-1-yl)methyl]-n-(2-hydroxyethyl)-n-methoxy-3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound S1C=2N(CC(C)C)C(=O)N(C)C(=O)C=2C(C(=O)N(CCO)OC)=C1CN1C(C)=NC(Cl)=C1Cl COWXFPKRNKUORL-UHFFFAOYSA-N 0.000 claims description 3
• VIDVFTXECDAGAM-UHFFFAOYSA-N 6-[(4,5-dichloro-2-methylimidazol-1-yl)methyl]-n-ethyl-n-methoxy-3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound S1C=2N(CC(C)C)C(=O)N(C)C(=O)C=2C(C(=O)N(OC)CC)=C1CN1C(C)=NC(Cl)=C1Cl VIDVFTXECDAGAM-UHFFFAOYSA-N 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 230000005764 inhibitory process Effects 0.000 claims description 3
• OOYOTIJOKDITGB-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-5-carboxamide Chemical compound S1C=2N(CC(C)C)C(=O)N(C)C(=O)C=2C(C(=O)N(C)OC)=C1CC1=CC=CC=C1C(F)(F)F OOYOTIJOKDITGB-UHFFFAOYSA-N 0.000 claims description 3
• ROPZMWZSGVUPET-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-6-[(2-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CN=C3NC=1C)=C2C(=O)N(C)OC ROPZMWZSGVUPET-UHFFFAOYSA-N 0.000 claims description 3
• BZKSHTJFQWYDQL-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-6-[(2-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-2,4-dioxo-1-propan-2-ylthieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)N1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CN=C3NC=1C)=C2C(=O)N(C)OC BZKSHTJFQWYDQL-UHFFFAOYSA-N 0.000 claims description 3
• VZMVSPBAUSGBBT-UHFFFAOYSA-N 6-[[4,5-dichloro-2-(hydroxymethyl)imidazol-1-yl]methyl]-n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound S1C=2N(CC(C)C)C(=O)N(C)C(=O)C=2C(C(=O)N(C)OC)=C1CN1C(CO)=NC(Cl)=C1Cl VZMVSPBAUSGBBT-UHFFFAOYSA-N 0.000 claims description 2
• 125000003277 amino group Chemical group 0.000 claims description 2
• 125000001589 carboacyl group Chemical group 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• PTPSSOFZIVWMFL-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-(quinolin-4-ylmethyl)thieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CC=C3N=CC=1)=C2C(=O)N(C)OC PTPSSOFZIVWMFL-UHFFFAOYSA-N 0.000 claims description 2
• AYZHIPAPDNBZJQ-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-6-[(2-propan-2-ylimidazol-1-yl)methyl]thieno[2,3-d]pyrimidine-5-carboxamide Chemical compound S1C=2N(CC(C)C)C(=O)N(C)C(=O)C=2C(C(=O)N(C)OC)=C1CN1C=CN=C1C(C)C AYZHIPAPDNBZJQ-UHFFFAOYSA-N 0.000 claims description 2
• JLTFCEWEQXCIRD-UHFFFAOYSA-N n-methoxy-n,3-dimethyl-1-(2-methylpropyl)-6-(2-methylsulfanylbenzimidazol-1-yl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound CSC1=NC2=CC=CC=C2N1C1=C(C(=O)N(C)OC)C(C(=O)N(C)C(=O)N2CC(C)C)=C2S1 JLTFCEWEQXCIRD-UHFFFAOYSA-N 0.000 claims description 2
• 239000002671 adjuvant Substances 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 208000023275 Autoimmune disease Diseases 0.000 abstract description 6
• 239000005864 Sulphur Chemical group 0.000 abstract 1
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• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 135
• 239000000047 product Substances 0.000 description 112
• 238000004949 mass spectrometry Methods 0.000 description 107
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 91
• 239000000243 solution Substances 0.000 description 64
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 62
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
• 239000007787 solid Substances 0.000 description 43
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 40
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
• 239000000203 mixture Substances 0.000 description 35
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 23
• 206010039083 rhinitis Diseases 0.000 description 22
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
• 229910004298 SiO 2 Inorganic materials 0.000 description 20
• 125000002252 acyl group Chemical group 0.000 description 20
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