TW200412959A - Isoquinoline compounds and medicinal use thereof - Google Patents

Info

Publication number

TW200412959A

TW200412959A TW092132796A TW92132796A TW200412959A TW 200412959 A TW200412959 A TW 200412959A TW 092132796 A TW092132796 A TW 092132796A TW 92132796 A TW92132796 A TW 92132796A TW 200412959 A TW200412959 A TW 200412959A

Authority

TW

Taiwan

Prior art keywords

methyl

group

isoquinoline

chloro

isod

Prior art date

2002-11-22

Links

• Espacenet
• Global Dossier
• Discuss

• 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title abstract 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 108
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 83
• 150000003839 salts Chemical class 0.000 claims abstract description 60
• 239000012453 solvate Substances 0.000 claims abstract description 42
• 206010008118 cerebral infarction Diseases 0.000 claims abstract description 14
• 208000026106 cerebrovascular disease Diseases 0.000 claims abstract description 14
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 10
• 150000004677 hydrates Chemical class 0.000 claims abstract description 10
• 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 claims abstract description 9
• 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 claims abstract description 9
• 201000010099 disease Diseases 0.000 claims abstract description 9
• 230000003449 preventive effect Effects 0.000 claims abstract description 8
• 230000001154 acute effect Effects 0.000 claims abstract description 6
• -1 quinoline compound Chemical class 0.000 claims description 461
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 163
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 137
• AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 123
• 125000001424 substituent group Chemical group 0.000 claims description 99
• 125000004432 carbon atom Chemical group C* 0.000 claims description 96
• 125000000217 alkyl group Chemical group 0.000 claims description 93
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 92
• 239000002904 solvent Substances 0.000 claims description 87
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 75
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 64
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 64
• 229910052799 carbon Inorganic materials 0.000 claims description 64
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 62
• 125000003277 amino group Chemical group 0.000 claims description 57
• SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 46
• XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 claims description 44
• LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 claims description 41
• 239000013543 active substance Substances 0.000 claims description 39
• 229910052757 nitrogen Inorganic materials 0.000 claims description 37
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 35
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 35
• 150000007857 hydrazones Chemical class 0.000 claims description 34
• 150000002576 ketones Chemical class 0.000 claims description 30
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 30
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 29
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
• 150000003254 radicals Chemical class 0.000 claims description 29
• 125000001072 heteroaryl group Chemical group 0.000 claims description 28
• 229910052801 chlorine Inorganic materials 0.000 claims description 27
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 26
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 25
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
• 125000003118 aryl group Chemical group 0.000 claims description 23
• 229960000948 quinine Drugs 0.000 claims description 22
• 235000001258 Cinchona calisaya Nutrition 0.000 claims description 21
• 125000003545 alkoxy group Chemical group 0.000 claims description 21
• LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 claims description 21
• 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims description 20
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 20
• 125000005843 halogen group Chemical group 0.000 claims description 20
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 19
• 125000002947 alkylene group Chemical group 0.000 claims description 19
• 239000003814 drug Substances 0.000 claims description 19
• ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 18
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 16
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 16
• 229910052731 fluorine Inorganic materials 0.000 claims description 15
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 14
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 13
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 13
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
• 125000001153 fluoro group Chemical group F* 0.000 claims description 12
• YYFLDZZDOUDZQM-UHFFFAOYSA-N 3-[1-[[4-(3-phenylquinolin-2-yl)phenyl]methyl]piperidin-4-yl]-1h-benzimidazol-2-one Chemical compound O=C1NC2=CC=CC=C2N1C(CC1)CCN1CC(C=C1)=CC=C1C1=NC2=CC=CC=C2C=C1C1=CC=CC=C1 YYFLDZZDOUDZQM-UHFFFAOYSA-N 0.000 claims description 11
• 150000001412 amines Chemical group 0.000 claims description 11
• 239000000460 chlorine Substances 0.000 claims description 11
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
• 125000003396 thiol group Chemical class [H]S* 0.000 claims description 11
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 10
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 10
• 239000007789 gas Substances 0.000 claims description 10
• PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims description 9
• 239000000126 substance Substances 0.000 claims description 9
• 229940124597 therapeutic agent Drugs 0.000 claims description 9
• UTBULQCHEUWJNV-UHFFFAOYSA-N 4-phenylpiperidine Chemical compound C1CNCCC1C1=CC=CC=C1 UTBULQCHEUWJNV-UHFFFAOYSA-N 0.000 claims description 8
• 150000001335 aliphatic alkanes Chemical group 0.000 claims description 8
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
• 229910052760 oxygen Inorganic materials 0.000 claims description 8
• 239000001301 oxygen Substances 0.000 claims description 8
• WTKZEGDFNFYCGP-UHFFFAOYSA-O Pyrazolium Chemical compound C1=CN[NH+]=C1 WTKZEGDFNFYCGP-UHFFFAOYSA-O 0.000 claims description 7
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 7
• 125000004414 alkyl thio group Chemical group 0.000 claims description 7
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 7
• 125000004434 sulfur atom Chemical group 0.000 claims description 7
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical group N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
• 125000000468 ketone group Chemical group 0.000 claims description 6
• 230000003287 optical effect Effects 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
• LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 claims description 5
• ZYYXQCXWHWJVCE-UHFFFAOYSA-N Cl.C1=NC=CC=2C(CC=CC12)=O Chemical compound Cl.C1=NC=CC=2C(CC=CC12)=O ZYYXQCXWHWJVCE-UHFFFAOYSA-N 0.000 claims description 5
• 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 5
• 125000003282 alkyl amino group Chemical group 0.000 claims description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
• VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 claims description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
• 125000004043 oxo group Chemical group O=* 0.000 claims description 5
• JJBMNZQPKITTTG-UHFFFAOYSA-N 2-methyl-1,2-thiazol-2-ium Chemical compound C[N+]1=CC=CS1 JJBMNZQPKITTTG-UHFFFAOYSA-N 0.000 claims description 4
• UZOFELREXGAFOI-UHFFFAOYSA-N 4-methylpiperidine Chemical compound CC1CCNCC1 UZOFELREXGAFOI-UHFFFAOYSA-N 0.000 claims description 4
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 4
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
• ZDQCLDBVVQUHDH-UHFFFAOYSA-N 6h-isoquinolin-5-one Chemical compound N1=CC=C2C(=O)CC=CC2=C1 ZDQCLDBVVQUHDH-UHFFFAOYSA-N 0.000 claims description 3
• VIZLFJHYMGLHKQ-UHFFFAOYSA-N 9H-fluorene 1H-pyrazole Chemical compound N1N=CC=C1.C1=CC=CC=2C3=CC=CC=C3CC12 VIZLFJHYMGLHKQ-UHFFFAOYSA-N 0.000 claims description 3
• WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 claims description 3
• 238000005576 amination reaction Methods 0.000 claims description 3
• 239000011737 fluorine Substances 0.000 claims description 3
• 239000004312 hexamethylene tetramine Substances 0.000 claims description 3
• 235000010299 hexamethylene tetramine Nutrition 0.000 claims description 3
• VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 claims description 3
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 3
• HVVNJUAVDAZWCB-UHFFFAOYSA-N prolinol Chemical compound OCC1CCCN1 HVVNJUAVDAZWCB-UHFFFAOYSA-N 0.000 claims description 3
• IYLGZMTXKJYONK-ACLXAEORSA-N (12s,15r)-15-hydroxy-11,16-dioxo-15,20-dihydrosenecionan-12-yl acetate Chemical class O1C(=O)[C@](CC)(O)C[C@@H](C)[C@](C)(OC(C)=O)C(=O)OCC2=CCN3[C@H]2[C@H]1CC3 IYLGZMTXKJYONK-ACLXAEORSA-N 0.000 claims description 2
• YJRMHIKEMDTYDR-UHFFFAOYSA-N 2-methylisoquinolin-1-one Chemical compound C1=CC=C2C(=O)N(C)C=CC2=C1 YJRMHIKEMDTYDR-UHFFFAOYSA-N 0.000 claims description 2
• PQOJDQVCYMPPRV-UHFFFAOYSA-N 3-ethyl-2-methylisoquinolin-1-one Chemical compound CN1C(C2=CC=CC=C2C=C1CC)=O PQOJDQVCYMPPRV-UHFFFAOYSA-N 0.000 claims description 2
• 239000004215 Carbon black (E152) Substances 0.000 claims description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
• AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 claims description 2
• 229930195733 hydrocarbon Natural products 0.000 claims description 2
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
• IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical group CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 claims description 2
• JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 claims description 2
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims 3
• MCGBIXXDQFWVDW-UHFFFAOYSA-N 4,5-dihydro-1h-pyrazole Chemical compound C1CC=NN1 MCGBIXXDQFWVDW-UHFFFAOYSA-N 0.000 claims 2
• UCRIXEWTILHNCG-UHFFFAOYSA-N 1-ethyl-2h-pyridine Chemical compound CCN1CC=CC=C1 UCRIXEWTILHNCG-UHFFFAOYSA-N 0.000 claims 1
• HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 claims 1
• KOFZWWMCDUHEEM-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound [CH2]N1CCCC1 KOFZWWMCDUHEEM-UHFFFAOYSA-N 0.000 claims 1
• CMVIZARQTOGMMI-UHFFFAOYSA-N 2-methyl-1H-hexazine Chemical compound CN1NN=NN=N1 CMVIZARQTOGMMI-UHFFFAOYSA-N 0.000 claims 1
• IPGQTAJSHBBRMY-UHFFFAOYSA-N 2-methyl-3-propan-2-ylisoquinolin-1-one Chemical compound C1=CC=C2C(=O)N(C)C(C(C)C)=CC2=C1 IPGQTAJSHBBRMY-UHFFFAOYSA-N 0.000 claims 1
• BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 claims 1
• QFRZXJXJPKWIHW-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-3-methyl-2h-isoquinolin-1-one Chemical compound C1=CC=C2C(CN(C)C)=C(C)NC(=O)C2=C1 QFRZXJXJPKWIHW-UHFFFAOYSA-N 0.000 claims 1
• JFTOHNBEOLJHBC-UHFFFAOYSA-N 4-piperidin-4-yl-2h-isoquinolin-1-one Chemical compound C12=CC=CC=C2C(=O)NC=C1C1CCNCC1 JFTOHNBEOLJHBC-UHFFFAOYSA-N 0.000 claims 1
• XKVUYEYANWFIJX-UHFFFAOYSA-N 5-methyl-1h-pyrazole Chemical compound CC1=CC=NN1 XKVUYEYANWFIJX-UHFFFAOYSA-N 0.000 claims 1
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
• 239000005977 Ethylene Substances 0.000 claims 1
• JLESPOKBPILILK-UHFFFAOYSA-N [O-][N+](=O)[C]C#N Chemical group [O-][N+](=O)[C]C#N JLESPOKBPILILK-UHFFFAOYSA-N 0.000 claims 1
• 125000003368 amide group Chemical group 0.000 claims 1
• 125000000747 amidyl group Chemical group [H][N-]* 0.000 claims 1
• 229910021529 ammonia Inorganic materials 0.000 claims 1
• 125000005140 aralkylsulfonyl group Chemical group 0.000 claims 1
• 229910052797 bismuth Inorganic materials 0.000 claims 1
• JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 claims 1
• 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims 1
• 235000019441 ethanol Nutrition 0.000 claims 1
• 125000004404 heteroalkyl group Chemical group 0.000 claims 1
• 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
• DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 claims 1
• YWXLSHOWXZUMSR-UHFFFAOYSA-N octan-4-one Chemical compound CCCCC(=O)CCC YWXLSHOWXZUMSR-UHFFFAOYSA-N 0.000 claims 1
• 230000000069 prophylactic effect Effects 0.000 claims 1
• 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims 1
• VSRBKQFNFZQRBM-UHFFFAOYSA-N tuaminoheptane Chemical compound CCCCCC(C)N VSRBKQFNFZQRBM-UHFFFAOYSA-N 0.000 claims 1
• 239000003112 inhibitor Substances 0.000 abstract 1
• 238000003786 synthesis reaction Methods 0.000 description 203
• 230000015572 biosynthetic process Effects 0.000 description 201
• 238000006243 chemical reaction Methods 0.000 description 201
• 239000002994 raw material Substances 0.000 description 195
• 238000000034 method Methods 0.000 description 191
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 139
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 116
• 238000005481 NMR spectroscopy Methods 0.000 description 88
• 238000005160 1H NMR spectroscopy Methods 0.000 description 66
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 66
• 239000000243 solution Substances 0.000 description 66
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 63
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 61
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 56
• 238000010992 reflux Methods 0.000 description 53
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
• 239000013078 crystal Substances 0.000 description 46
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 46
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 43
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 39
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 37
• RXMRGBVLCSYIBO-UHFFFAOYSA-M tetramethylazanium;iodide Chemical compound [I-].C[N+](C)(C)C RXMRGBVLCSYIBO-UHFFFAOYSA-M 0.000 description 36
• 239000002585 base Substances 0.000 description 35
• 101150041968 CDC13 gene Proteins 0.000 description 33
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 33
• 229910052739 hydrogen Inorganic materials 0.000 description 32
• IHCCLXNEEPMSIO-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 IHCCLXNEEPMSIO-UHFFFAOYSA-N 0.000 description 31
• 239000000203 mixture Substances 0.000 description 31
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 28
• 235000019341 magnesium sulphate Nutrition 0.000 description 28
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
• 238000001914 filtration Methods 0.000 description 23
• 229910000027 potassium carbonate Inorganic materials 0.000 description 23
• 235000011181 potassium carbonates Nutrition 0.000 description 23
• 239000007864 aqueous solution Substances 0.000 description 22
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