TWI419889B - 吡唑并〔１，５-ａ〕嘧啶化合物 - Google Patents

Info

Publication number

TWI419889B

TWI419889B TW96122242A TW96122242A TWI419889B TW I419889 B TWI419889 B TW I419889B TW 96122242 A TW96122242 A TW 96122242A TW 96122242 A TW96122242 A TW 96122242A TW I419889 B TWI419889 B TW I419889B

Authority

TW

Taiwan

Prior art keywords

group

chlorophenyl

pyrimidine

alkyl

pyrazolo

Prior art date

2006-07-05

Links

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• Global Dossier
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• -1 pyrazolo [1,5-a] pyrimidine compound Chemical class 0.000 title claims description 114
• 150000001875 compounds Chemical class 0.000 claims description 383
• 125000000217 alkyl group Chemical group 0.000 claims description 209
• LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical compound N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 claims description 167
• 125000005843 halogen group Chemical group 0.000 claims description 99
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 79
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 68
• 150000001412 amines Chemical group 0.000 claims description 60
• 229920006395 saturated elastomer Polymers 0.000 claims description 60
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 56
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 51
• 125000003277 amino group Chemical group 0.000 claims description 50
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 49
• 125000003545 alkoxy group Chemical group 0.000 claims description 46
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 46
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 42
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 42
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 34
• 150000003839 salts Chemical class 0.000 claims description 33
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 32
• 229910052717 sulfur Inorganic materials 0.000 claims description 31
• 125000001424 substituent group Chemical group 0.000 claims description 27
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 26
• 125000004385 trihaloalkyl group Chemical group 0.000 claims description 26
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 25
• 125000004076 pyridyl group Chemical group 0.000 claims description 23
• 229910052757 nitrogen Inorganic materials 0.000 claims description 22
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 20
• 125000002950 monocyclic group Chemical group 0.000 claims description 18
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 18
• 239000003795 chemical substances by application Substances 0.000 claims description 17
• 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 claims description 16
• 125000004434 sulfur atom Chemical group 0.000 claims description 16
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 15
• 125000005842 heteroatom Chemical group 0.000 claims description 15
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 15
• 125000004432 carbon atom Chemical group C* 0.000 claims description 13
• 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 claims description 12
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 12
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
• 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 11
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
• 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 11
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 9
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 9
• 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 8
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 8
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 8
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 7
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 7
• 229910052799 carbon Inorganic materials 0.000 claims description 7
• 238000011282 treatment Methods 0.000 claims description 7
• 201000010099 disease Diseases 0.000 claims description 6
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 5
• 208000035475 disorder Diseases 0.000 claims description 5
• 208000011117 substance-related disease Diseases 0.000 claims description 5
• 208000024827 Alzheimer disease Diseases 0.000 claims description 4
• 230000000202 analgesic effect Effects 0.000 claims description 4
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 4
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 4
• 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 3
• 208000007848 Alcoholism Diseases 0.000 claims description 3
• 208000019901 Anxiety disease Diseases 0.000 claims description 3
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
• 206010013654 Drug abuse Diseases 0.000 claims description 3
• 208000008589 Obesity Diseases 0.000 claims description 3
• 208000022531 anorexia Diseases 0.000 claims description 3
• 230000036506 anxiety Effects 0.000 claims description 3
• 230000002490 cerebral effect Effects 0.000 claims description 3
• 206010061428 decreased appetite Diseases 0.000 claims description 3
• 229940079593 drug Drugs 0.000 claims description 3
• 239000003623 enhancer Substances 0.000 claims description 3
• 235000020824 obesity Nutrition 0.000 claims description 3
• 201000000980 schizophrenia Diseases 0.000 claims description 3
• 230000005586 smoking cessation Effects 0.000 claims description 3
• 229940124597 therapeutic agent Drugs 0.000 claims description 3
• 239000013598 vector Substances 0.000 claims description 3
• 208000000044 Amnesia Diseases 0.000 claims description 2
• 208000031091 Amnestic disease Diseases 0.000 claims description 2
• 208000027559 Appetite disease Diseases 0.000 claims description 2
• 208000020925 Bipolar disease Diseases 0.000 claims description 2
• 229940123158 Cannabinoid CB1 receptor antagonist Drugs 0.000 claims description 2
• 208000028698 Cognitive impairment Diseases 0.000 claims description 2
• 208000016192 Demyelinating disease Diseases 0.000 claims description 2
• 206010012735 Diarrhoea Diseases 0.000 claims description 2
• 208000012661 Dyskinesia Diseases 0.000 claims description 2
• 208000014094 Dystonic disease Diseases 0.000 claims description 2
• 206010014612 Encephalitis viral Diseases 0.000 claims description 2
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 2
• 206010016654 Fibrosis Diseases 0.000 claims description 2
• 208000018522 Gastrointestinal disease Diseases 0.000 claims description 2
• 208000010412 Glaucoma Diseases 0.000 claims description 2
• 208000032456 Hemorrhagic Shock Diseases 0.000 claims description 2
• 208000023105 Huntington disease Diseases 0.000 claims description 2
• 208000001953 Hypotension Diseases 0.000 claims description 2
• 206010061218 Inflammation Diseases 0.000 claims description 2
• 208000019695 Migraine disease Diseases 0.000 claims description 2
• 206010028980 Neoplasm Diseases 0.000 claims description 2
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 2
• 206010033664 Panic attack Diseases 0.000 claims description 2
• 208000018737 Parkinson disease Diseases 0.000 claims description 2
• 206010039966 Senile dementia Diseases 0.000 claims description 2
• 206010040070 Septic Shock Diseases 0.000 claims description 2
• 206010049771 Shock haemorrhagic Diseases 0.000 claims description 2
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 2
• 206010044565 Tremor Diseases 0.000 claims description 2
• 206010047700 Vomiting Diseases 0.000 claims description 2
• 230000006986 amnesia Effects 0.000 claims description 2
• 208000006673 asthma Diseases 0.000 claims description 2
• 201000011510 cancer Diseases 0.000 claims description 2
• 239000003555 cannabinoid 1 receptor antagonist Substances 0.000 claims description 2
• 230000001684 chronic effect Effects 0.000 claims description 2
• 230000007882 cirrhosis Effects 0.000 claims description 2
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 2
• 208000010877 cognitive disease Diseases 0.000 claims description 2
• 230000003111 delayed effect Effects 0.000 claims description 2
• 208000010118 dystonia Diseases 0.000 claims description 2
• 206010015037 epilepsy Diseases 0.000 claims description 2
• 230000036543 hypotension Effects 0.000 claims description 2
• 208000026278 immune system disease Diseases 0.000 claims description 2
• 208000015181 infectious disease Diseases 0.000 claims description 2
• 208000000509 infertility Diseases 0.000 claims description 2
• 230000036512 infertility Effects 0.000 claims description 2
• 231100000535 infertility Toxicity 0.000 claims description 2
• 230000004054 inflammatory process Effects 0.000 claims description 2
• 206010022437 insomnia Diseases 0.000 claims description 2
• 206010027599 migraine Diseases 0.000 claims description 2
• 201000006417 multiple sclerosis Diseases 0.000 claims description 2
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
• 208000019906 panic disease Diseases 0.000 claims description 2
• 208000033808 peripheral neuropathy Diseases 0.000 claims description 2
• 208000020016 psychiatric disease Diseases 0.000 claims description 2
• 230000036303 septic shock Effects 0.000 claims description 2
• 230000000391 smoking effect Effects 0.000 claims description 2
• 230000002992 thymic effect Effects 0.000 claims description 2
• 125000004953 trihalomethyl group Chemical group 0.000 claims description 2
• 201000002498 viral encephalitis Diseases 0.000 claims description 2
• 230000008673 vomiting Effects 0.000 claims description 2
• 239000008194 pharmaceutical composition Substances 0.000 claims 6
• SMQAQNWCDKDKKO-UHFFFAOYSA-N 2-methylpyrazolo[1,5-a]pyrimidine Chemical compound N1=CC=CN2N=C(C)C=C21 SMQAQNWCDKDKKO-UHFFFAOYSA-N 0.000 claims 1
• 208000032841 Bulimia Diseases 0.000 claims 1
• 206010006550 Bulimia nervosa Diseases 0.000 claims 1
• 206010012335 Dependence Diseases 0.000 claims 1
• 208000036110 Neuroinflammatory disease Diseases 0.000 claims 1
• 206010057852 Nicotine dependence Diseases 0.000 claims 1
• 208000003782 Raynaud disease Diseases 0.000 claims 1
• 208000012322 Raynaud phenomenon Diseases 0.000 claims 1
• 208000025569 Tobacco Use disease Diseases 0.000 claims 1
• 208000000323 Tourette Syndrome Diseases 0.000 claims 1
• 208000016620 Tourette disease Diseases 0.000 claims 1
• 208000030886 Traumatic Brain injury Diseases 0.000 claims 1
• 239000004480 active ingredient Substances 0.000 claims 1
• IYCUCQGVEZOMMV-UHFFFAOYSA-N aminomethanethiol Chemical compound NCS IYCUCQGVEZOMMV-UHFFFAOYSA-N 0.000 claims 1
• 230000003444 anaesthetic effect Effects 0.000 claims 1
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
• 230000000968 intestinal effect Effects 0.000 claims 1
• 238000004519 manufacturing process Methods 0.000 claims 1
• 206010027175 memory impairment Diseases 0.000 claims 1
• VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 claims 1
• 230000003959 neuroinflammation Effects 0.000 claims 1
• 230000003449 preventive effect Effects 0.000 claims 1
• BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 claims 1
• 150000003573 thiols Chemical class 0.000 claims 1
• 208000014001 urinary system disease Diseases 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 299
• 239000000243 solution Substances 0.000 description 154
• 239000000203 mixture Substances 0.000 description 152
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 138
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 119
• 235000019439 ethyl acetate Nutrition 0.000 description 114
• 239000002904 solvent Substances 0.000 description 111
• 239000011541 reaction mixture Substances 0.000 description 106
• 239000000843 powder Substances 0.000 description 89
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 82
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 78
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 76
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 74
• 239000012044 organic layer Substances 0.000 description 72
• 239000012043 crude product Substances 0.000 description 71
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
• 238000006243 chemical reaction Methods 0.000 description 60
• 239000000706 filtrate Substances 0.000 description 54
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
• 238000001816 cooling Methods 0.000 description 52
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
• 125000000623 heterocyclic group Chemical group 0.000 description 51
• 238000004440 column chromatography Methods 0.000 description 48
• 239000007787 solid Substances 0.000 description 46
• 239000002585 base Substances 0.000 description 45
• 239000007858 starting material Substances 0.000 description 42
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 37
• 235000019341 magnesium sulphate Nutrition 0.000 description 37
• IUVCFHHAEHNCFT-INIZCTEOSA-N 2-[(1s)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one Chemical compound C1=C(F)C(OC(C)C)=CC=C1C(C1=C(N)N=CN=C11)=NN1[C@@H](C)C1=C(C=2C=C(F)C=CC=2)C(=O)C2=CC(F)=CC=C2O1 IUVCFHHAEHNCFT-INIZCTEOSA-N 0.000 description 36
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 31
• 238000000034 method Methods 0.000 description 31
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
• 235000019441 ethanol Nutrition 0.000 description 27
• 125000003118 aryl group Chemical group 0.000 description 25
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
• 238000003756 stirring Methods 0.000 description 22
• 239000007795 chemical reaction product Substances 0.000 description 21
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
• 238000001914 filtration Methods 0.000 description 20
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 19
• 239000002244 precipitate Substances 0.000 description 19
• 239000012267 brine Substances 0.000 description 18
• 125000000753 cycloalkyl group Chemical group 0.000 description 18
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
• 229960004132 diethyl ether Drugs 0.000 description 17
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 15
• 239000000741 silica gel Substances 0.000 description 15
• 229910002027 silica gel Inorganic materials 0.000 description 15
• 239000011593 sulfur Substances 0.000 description 15
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
• 125000000468 ketone group Chemical group 0.000 description 14
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
• NMVVJZXGEJPLBD-UHFFFAOYSA-N tert-butyl n-(1-carbamoylcyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1(C(N)=O)CCCCC1 NMVVJZXGEJPLBD-UHFFFAOYSA-N 0.000 description 14
• NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 14
• 239000000499 gel Substances 0.000 description 13
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
• 125000001072 heteroaryl group Chemical group 0.000 description 12
• 239000002253 acid Substances 0.000 description 11
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 11
• 125000004103 aminoalkyl group Chemical group 0.000 description 11
• 125000002619 bicyclic group Chemical group 0.000 description 11
• KAMHJIGNJYVODO-UHFFFAOYSA-N S(=O)(=O)=C1NN2C(N=CC=C2)=C1 Chemical compound S(=O)(=O)=C1NN2C(N=CC=C2)=C1 KAMHJIGNJYVODO-UHFFFAOYSA-N 0.000 description 10
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 10
• 125000004414 alkyl thio group Chemical group 0.000 description 10
• 125000004663 dialkyl amino group Chemical group 0.000 description 10
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• 239000003054 catalyst Substances 0.000 description 9
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 9
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
• 125000002757 morpholinyl group Chemical group 0.000 description 9
• 125000003386 piperidinyl group Chemical group 0.000 description 9
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 9
• 238000010898 silica gel chromatography Methods 0.000 description 9
• 229910052938 sodium sulfate Inorganic materials 0.000 description 9
• 235000011152 sodium sulphate Nutrition 0.000 description 9
• 102000018208 Cannabinoid Receptor Human genes 0.000 description 8
• 108050007331 Cannabinoid receptor Proteins 0.000 description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
• 239000013078 crystal Substances 0.000 description 8
• 125000005265 dialkylamine group Chemical group 0.000 description 8
• 229910052760 oxygen Inorganic materials 0.000 description 8
• 239000001301 oxygen Substances 0.000 description 8
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 7
• 230000002140 halogenating effect Effects 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• 229910052763 palladium Inorganic materials 0.000 description 7
• 229910000027 potassium carbonate Inorganic materials 0.000 description 7
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 6
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
• 239000000654 additive Substances 0.000 description 6
• 230000000996 additive effect Effects 0.000 description 6
• 125000003282 alkyl amino group Chemical group 0.000 description 6
• 125000002947 alkylene group Chemical group 0.000 description 6
• 235000019270 ammonium chloride Nutrition 0.000 description 6
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 6
• 239000000872 buffer Substances 0.000 description 6
• 125000004181 carboxyalkyl group Chemical group 0.000 description 6
• 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 6
• 239000010410 layer Substances 0.000 description 6
• 239000012299 nitrogen atmosphere Substances 0.000 description 6
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
• 235000017557 sodium bicarbonate Nutrition 0.000 description 6
• 229910000029 sodium carbonate Inorganic materials 0.000 description 6
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
• 125000003107 substituted aryl group Chemical group 0.000 description 6
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
• RSPCKAHMRANGJZ-UHFFFAOYSA-N thiohydroxylamine Chemical compound SN RSPCKAHMRANGJZ-UHFFFAOYSA-N 0.000 description 6
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