HRP20020960A2 - 2-aminocarbonyl-9h-purine derivatives - Google Patents

Info

Publication number

HRP20020960A2

HRP20020960A2 HR20020960A HRP20020960A HRP20020960A2 HR P20020960 A2 HRP20020960 A2 HR P20020960A2 HR 20020960 A HR20020960 A HR 20020960A HR P20020960 A HRP20020960 A HR P20020960A HR P20020960 A2 HRP20020960 A2 HR P20020960A2

Authority

HR

Croatia

Prior art keywords

alkyl

formula

compound

optionally substituted

amino

Prior art date

2000-06-06

Links

• Espacenet
• Global Dossier
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• BMHHQPYFORGXQA-UHFFFAOYSA-N 7h-purine-2-carboxamide Chemical class NC(=O)C1=NC=C2N=CNC2=N1 BMHHQPYFORGXQA-UHFFFAOYSA-N 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims description 331
• 238000002360 preparation method Methods 0.000 claims description 213
• -1 homopiperidin -3-yl Chemical group 0.000 claims description 134
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 92
• 238000000034 method Methods 0.000 claims description 79
• 238000006243 chemical reaction Methods 0.000 claims description 60
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 60
• 150000003839 salts Chemical class 0.000 claims description 59
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 58
• 229910052799 carbon Inorganic materials 0.000 claims description 54
• 229910052757 nitrogen Inorganic materials 0.000 claims description 46
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 42
• 125000006239 protecting group Chemical group 0.000 claims description 39
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 37
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 36
• 239000012453 solvate Substances 0.000 claims description 34
• 229910052739 hydrogen Inorganic materials 0.000 claims description 31
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 29
• 238000011282 treatment Methods 0.000 claims description 28
• 150000001412 amines Chemical class 0.000 claims description 26
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 25
• 125000004432 carbon atom Chemical group C* 0.000 claims description 24
• 229910052736 halogen Inorganic materials 0.000 claims description 23
• 150000002367 halogens Chemical class 0.000 claims description 23
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 22
• 125000002947 alkylene group Chemical group 0.000 claims description 21
• 239000003054 catalyst Substances 0.000 claims description 20
• 125000000579 2,2-diphenylethyl 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])C([H])([H])* 0.000 claims description 17
• 241000124008 Mammalia Species 0.000 claims description 17
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 17
• 201000010099 disease Diseases 0.000 claims description 15
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 14
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 13
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 13
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 12
• 201000004624 Dermatitis Diseases 0.000 claims description 12
• 208000007882 Gastritis Diseases 0.000 claims description 12
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 12
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 12
• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 12
• 208000010668 atopic eczema Diseases 0.000 claims description 12
• 125000002393 azetidinyl group Chemical group 0.000 claims description 12
• 206010006451 bronchitis Diseases 0.000 claims description 12
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 12
• 125000003386 piperidinyl group Chemical group 0.000 claims description 12
• 239000003814 drug Substances 0.000 claims description 11
• 238000004519 manufacturing process Methods 0.000 claims description 11
• 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 description 11
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 10
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 10
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 10
• 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 10
• 125000004263 tetrahydroisoquinolin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])C2=C([H])C([H])=C([H])C([H])=C2C1([H])* 0.000 claims description 10
• 101150051188 Adora2a gene Proteins 0.000 claims description 9
• 125000001589 carboacyl group Chemical group 0.000 claims description 9
• 241000894006 Bacteria Species 0.000 claims description 8
• 208000006673 asthma Diseases 0.000 claims description 8
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
• 125000001624 naphthyl group Chemical group 0.000 claims description 8
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 8
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 7
• 230000006378 damage Effects 0.000 claims description 7
• 229940079593 drug Drugs 0.000 claims description 7
• 125000005842 heteroatom Chemical group 0.000 claims description 7
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
• 239000001301 oxygen Substances 0.000 claims description 7
• 229910052760 oxygen Inorganic materials 0.000 claims description 7
• 230000008569 process Effects 0.000 claims description 7
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
• 201000006474 Brain Ischemia Diseases 0.000 claims description 6
• 206010006458 Bronchitis chronic Diseases 0.000 claims description 6
• 125000003031 C5-C7 cycloalkylene group Chemical group 0.000 claims description 6
• 206010008120 Cerebral ischaemia Diseases 0.000 claims description 6
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 6
• 206010009137 Chronic sinusitis Diseases 0.000 claims description 6
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 6
• 208000011231 Crohn disease Diseases 0.000 claims description 6
• 201000003883 Cystic fibrosis Diseases 0.000 claims description 6
• 206010012434 Dermatitis allergic Diseases 0.000 claims description 6
• 206010014561 Emphysema Diseases 0.000 claims description 6
• 208000010228 Erectile Dysfunction Diseases 0.000 claims description 6
• 208000007984 Female Infertility Diseases 0.000 claims description 6
• 206010020772 Hypertension Diseases 0.000 claims description 6
• 206010021928 Infertility female Diseases 0.000 claims description 6
• 208000007466 Male Infertility Diseases 0.000 claims description 6
• 201000004681 Psoriasis Diseases 0.000 claims description 6
• 208000028017 Psychotic disease Diseases 0.000 claims description 6
• 206010063837 Reperfusion injury Diseases 0.000 claims description 6
• 206010040070 Septic Shock Diseases 0.000 claims description 6
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 6
• 125000000217 alkyl group Chemical group 0.000 claims description 6
• 239000002260 anti-inflammatory agent Substances 0.000 claims description 6
• 201000008937 atopic dermatitis Diseases 0.000 claims description 6
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 6
• 201000009267 bronchiectasis Diseases 0.000 claims description 6
• 206010008118 cerebral infarction Diseases 0.000 claims description 6
• 208000007451 chronic bronchitis Diseases 0.000 claims description 6
• 201000009151 chronic rhinitis Diseases 0.000 claims description 6
• 208000027157 chronic rhinosinusitis Diseases 0.000 claims description 6
• 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 6
• 206010012601 diabetes mellitus Diseases 0.000 claims description 6
• 210000002249 digestive system Anatomy 0.000 claims description 6
• 206010015037 epilepsy Diseases 0.000 claims description 6
• 201000001881 impotence Diseases 0.000 claims description 6
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
• 201000006417 multiple sclerosis Diseases 0.000 claims description 6
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 6
• 125000004043 oxo group Chemical group O=* 0.000 claims description 6
• 210000002345 respiratory system Anatomy 0.000 claims description 6
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
• 206010039083 rhinitis Diseases 0.000 claims description 6
• 230000036303 septic shock Effects 0.000 claims description 6
• 125000001424 substituent group Chemical group 0.000 claims description 6
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
• 229940121363 anti-inflammatory agent Drugs 0.000 claims description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 238000009833 condensation Methods 0.000 claims description 5
• 230000005494 condensation Effects 0.000 claims description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
• 230000029663 wound healing Effects 0.000 claims description 5
• VXLJJPYWNSWXPX-NBCVKUGOSA-N (3ar,4r,6s,6as)-4-[6-(2,2-diphenylethylamino)-2-ethoxycarbonylpurin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxylic acid Chemical compound C=12N=CN([C@H]3[C@@H]4OC(C)(C)O[C@@H]4[C@H](O3)C(O)=O)C2=NC(C(=O)OCC)=NC=1NCC(C=1C=CC=CC=1)C1=CC=CC=C1 VXLJJPYWNSWXPX-NBCVKUGOSA-N 0.000 claims description 4
• 208000018262 Peripheral vascular disease Diseases 0.000 claims description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 4
• 125000000623 heterocyclic group Chemical group 0.000 claims description 4
• 125000004193 piperazinyl group Chemical group 0.000 claims description 4
• 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 claims description 4
• 229910052717 sulfur Inorganic materials 0.000 claims description 4
• 239000011593 sulfur Substances 0.000 claims description 4
• WXTOFTCCIXLSKC-UHFFFAOYSA-N 1-(2-aminoethyl)-3-(1-pyridin-2-ylpiperidin-4-yl)urea;dihydrochloride Chemical compound Cl.Cl.C1CC(NC(=O)NCCN)CCN1C1=CC=CC=N1 WXTOFTCCIXLSKC-UHFFFAOYSA-N 0.000 claims description 3
• GGBDMBQBMDMLGX-XTCMURJCSA-N 9-[(3ar,4r,6s,6as)-6-(ethylcarbamoyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-6-(2,2-diphenylethylamino)-n-[2-[(1-pyridin-2-ylpiperidin-4-yl)carbamoylamino]ethyl]purine-2-carboxamide Chemical compound N1=C(C(=O)NCCNC(=O)NC2CCN(CC2)C=2N=CC=CC=2)N=C2N([C@@H]3O[C@@H]([C@H]4OC(C)(C)O[C@H]43)C(=O)NCC)C=NC2=C1NCC(C=1C=CC=CC=1)C1=CC=CC=C1 GGBDMBQBMDMLGX-XTCMURJCSA-N 0.000 claims description 3
• WFAHDKDGQXTGQL-JTNFPWQOSA-N 9-[(3ar,4r,6s,6as)-6-(ethylcarbamoyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-6-(2,2-diphenylethylamino)purine-2-carboxylic acid Chemical compound N1=C(C(O)=O)N=C2N([C@@H]3O[C@@H]([C@H]4OC(C)(C)O[C@H]43)C(=O)NCC)C=NC2=C1NCC(C=1C=CC=CC=1)C1=CC=CC=C1 WFAHDKDGQXTGQL-JTNFPWQOSA-N 0.000 claims description 3
• 230000001270 agonistic effect Effects 0.000 claims description 3
• 125000003545 alkoxy group Chemical group 0.000 claims description 3
• 238000005910 aminocarbonylation reaction Methods 0.000 claims description 3
• 239000012752 auxiliary agent Substances 0.000 claims description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• RWJFUQDRQOIAAF-UHFFFAOYSA-N ethyl 6-(2,2-diphenylethylamino)-7h-purine-2-carboxylate Chemical compound C=12N=CNC2=NC(C(=O)OCC)=NC=1NCC(C=1C=CC=CC=1)C1=CC=CC=C1 RWJFUQDRQOIAAF-UHFFFAOYSA-N 0.000 claims description 3
• UXVIJLXEICIWMK-CRDHKZEPSA-N ethyl 9-[(2r,3r,4r,5r)-3,4-diacetyloxy-5-(acetyloxymethyl)oxolan-2-yl]-6-(2,2-diphenylethylamino)purine-2-carboxylate Chemical compound C=12N=CN([C@H]3[C@@H]([C@H](OC(C)=O)[C@@H](COC(C)=O)O3)OC(C)=O)C2=NC(C(=O)OCC)=NC=1NCC(C=1C=CC=CC=1)C1=CC=CC=C1 UXVIJLXEICIWMK-CRDHKZEPSA-N 0.000 claims description 3
• IQBHZSDHJDDFPF-RKCWLVDCSA-N ethyl 9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(2,2-diphenylethylamino)purine-2-carboxylate Chemical compound C=12N=CN([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=NC(C(=O)OCC)=NC=1NCC(C=1C=CC=CC=1)C1=CC=CC=C1 IQBHZSDHJDDFPF-RKCWLVDCSA-N 0.000 claims description 3
• ACHBLUPHQWRKOE-WBMMKZCBSA-N ethyl 9-[(3ar,4r,6r,6ar)-6-(hydroxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-6-(2,2-diphenylethylamino)purine-2-carboxylate Chemical compound C=12N=CN([C@H]3[C@@H]4OC(C)(C)O[C@@H]4[C@@H](CO)O3)C2=NC(C(=O)OCC)=NC=1NCC(C=1C=CC=CC=1)C1=CC=CC=C1 ACHBLUPHQWRKOE-WBMMKZCBSA-N 0.000 claims description 3
• FOMNDTRDTVQWCJ-FJRSXGRASA-N ethyl 9-[(3ar,4r,6s,6as)-6-(ethylcarbamoyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-6-(2,2-diphenylethylamino)purine-2-carboxylate Chemical compound N1=C(C(=O)OCC)N=C2N([C@@H]3O[C@@H]([C@H]4OC(C)(C)O[C@H]43)C(=O)NCC)C=NC2=C1NCC(C=1C=CC=CC=1)C1=CC=CC=C1 FOMNDTRDTVQWCJ-FJRSXGRASA-N 0.000 claims description 3
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 3
• 208000027866 inflammatory disease Diseases 0.000 claims description 3
• 210000005259 peripheral blood Anatomy 0.000 claims description 3
• 239000011886 peripheral blood Substances 0.000 claims description 3
• 229940044601 receptor agonist Drugs 0.000 claims description 3
• 239000000018 receptor agonist Substances 0.000 claims description 3
• YVSWMCHIHVFURN-UHFFFAOYSA-N tert-butyl n-[2-[(1-pyridin-2-ylpiperidin-4-yl)carbamoylamino]ethyl]carbamate Chemical compound C1CC(NC(=O)NCCNC(=O)OC(C)(C)C)CCN1C1=CC=CC=N1 YVSWMCHIHVFURN-UHFFFAOYSA-N 0.000 claims description 3
• 125000004955 1,4-cyclohexylene group Chemical group [H]C1([H])C([H])([H])C([H])([*:1])C([H])([H])C([H])([H])C1([H])[*:2] 0.000 claims description 2
• SZYKXWYPIRIZOZ-UHFFFAOYSA-N 1-(2-aminoethyl)-3-(1-pyridin-2-ylpiperidin-4-yl)urea Chemical compound C1CC(NC(=O)NCCN)CCN1C1=CC=CC=N1 SZYKXWYPIRIZOZ-UHFFFAOYSA-N 0.000 claims description 2
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 2
• SLASUOSJPVRJDB-BBJOTMRQSA-N 4-[[2-[[6-(2,2-diphenylethylamino)-9-[(2r,3r,4s,5s)-5-(ethylcarbamoyl)-3,4-dihydroxyoxolan-2-yl]purine-2-carbonyl]amino]ethylcarbamoylamino]methyl]benzoic acid Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(C(=O)NCCNC(=O)NCC=3C=CC(=CC=3)C(O)=O)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 SLASUOSJPVRJDB-BBJOTMRQSA-N 0.000 claims description 2
• 230000001741 anti-phlogistic effect Effects 0.000 claims description 2
• VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 claims description 2
• 125000004273 azetidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])C1([H])* 0.000 claims description 2
• 239000011737 fluorine Substances 0.000 claims description 2
• 229910052731 fluorine Inorganic materials 0.000 claims description 2
• 208000023504 respiratory system disease Diseases 0.000 claims description 2
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims 2
• 210000000936 intestine Anatomy 0.000 claims 1
• 239000008194 pharmaceutical composition Substances 0.000 claims 1
• 125000006413 ring segment Chemical group 0.000 claims 1
• ZOTHAEBAWXWVID-HXEFRTELSA-N uk-432,097 Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(C(=O)NCCNC(=O)NC3CCN(CC3)C=3N=CC=CC=3)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 ZOTHAEBAWXWVID-HXEFRTELSA-N 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 348
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 201
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 186
• 239000000243 solution Substances 0.000 description 123
• 239000002904 solvent Substances 0.000 description 114
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 112
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 102
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 99
• 239000000203 mixture Substances 0.000 description 92
• 238000005160 1H NMR spectroscopy Methods 0.000 description 91
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 76
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 69
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
• 235000019439 ethyl acetate Nutrition 0.000 description 62
• 229940093499 ethyl acetate Drugs 0.000 description 62
• 239000007787 solid Substances 0.000 description 62
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 48
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 47
• 239000007864 aqueous solution Substances 0.000 description 44
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 44
• 238000010992 reflux Methods 0.000 description 42
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 40
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
• 239000002253 acid Substances 0.000 description 35
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 33
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 33
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 31
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 31
• 239000000741 silica gel Substances 0.000 description 31
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• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 25
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