TW200815417A - New compounds II - Google Patents

Info

Publication number

TW200815417A

TW200815417A TW096122335A TW96122335A TW200815417A TW 200815417 A TW200815417 A TW 200815417A TW 096122335 A TW096122335 A TW 096122335A TW 96122335 A TW96122335 A TW 96122335A TW 200815417 A TW200815417 A TW 200815417A

Authority

TW

Taiwan

Prior art keywords

group

alkyl

amine

methyl

compound

Prior art date

2006-06-27

Links

• Espacenet
• Global Dossier
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• 150000001875 compounds Chemical class 0.000 title claims abstract description 201
• 238000000034 method Methods 0.000 claims abstract description 41
• 150000003839 salts Chemical class 0.000 claims abstract description 33
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
• 239000012458 free base Substances 0.000 claims abstract description 6
• 238000002560 therapeutic procedure Methods 0.000 claims abstract 2
• 125000000217 alkyl group Chemical group 0.000 claims description 178
• 125000000623 heterocyclic group Chemical group 0.000 claims description 129
• -1 Ci -3 Chemical group 0.000 claims description 116
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 70
• 125000002837 carbocyclic group Chemical group 0.000 claims description 63
• 102000001267 GSK3 Human genes 0.000 claims description 60
• 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 claims description 60
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 56
• 150000001412 amines Chemical class 0.000 claims description 53
• 125000005843 halogen group Chemical group 0.000 claims description 53
• 229910052799 carbon Inorganic materials 0.000 claims description 47
• 229910052739 hydrogen Inorganic materials 0.000 claims description 47
• 239000001257 hydrogen Substances 0.000 claims description 47
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 46
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 42
• 239000002585 base Substances 0.000 claims description 41
• 229910052757 nitrogen Inorganic materials 0.000 claims description 37
• 125000004452 carbocyclyl group Chemical group 0.000 claims description 36
• LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 claims description 36
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 28
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 27
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 25
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 22
• 210000000988 bone and bone Anatomy 0.000 claims description 21
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
• 150000002431 hydrogen Chemical group 0.000 claims description 21
• 241000124008 Mammalia Species 0.000 claims description 20
• 206010012289 Dementia Diseases 0.000 claims description 19
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
• 125000001188 haloalkyl group Chemical group 0.000 claims description 18
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
• 125000003545 alkoxy group Chemical group 0.000 claims description 17
• 239000007789 gas Substances 0.000 claims description 17
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
• 230000002265 prevention Effects 0.000 claims description 17
• 125000003396 thiol group Chemical class [H]S* 0.000 claims description 17
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 16
• 125000003118 aryl group Chemical group 0.000 claims description 16
• 201000010099 disease Diseases 0.000 claims description 16
• 239000003814 drug Substances 0.000 claims description 16
• 230000001965 increasing effect Effects 0.000 claims description 16
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 15
• 239000002253 acid Substances 0.000 claims description 15
• 125000003342 alkenyl group Chemical group 0.000 claims description 15
• 125000001153 fluoro group Chemical group F* 0.000 claims description 15
• 208000024891 symptom Diseases 0.000 claims description 15
• 208000024827 Alzheimer disease Diseases 0.000 claims description 14
• 208000001132 Osteoporosis Diseases 0.000 claims description 14
• 125000000304 alkynyl group Chemical group 0.000 claims description 13
• 238000004519 manufacturing process Methods 0.000 claims description 13
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 13
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 13
• 125000003277 amino group Chemical group 0.000 claims description 12
• 125000006239 protecting group Chemical group 0.000 claims description 12
• 206010017076 Fracture Diseases 0.000 claims description 11
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 11
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
• 201000000980 schizophrenia Diseases 0.000 claims description 11
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 10
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
• 125000004122 cyclic group Chemical group 0.000 claims description 10
• 230000011164 ossification Effects 0.000 claims description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 claims description 9
• 208000020925 Bipolar disease Diseases 0.000 claims description 9
• 208000010392 Bone Fractures Diseases 0.000 claims description 9
• 206010028980 Neoplasm Diseases 0.000 claims description 9
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 9
• 208000010877 cognitive disease Diseases 0.000 claims description 9
• 206010012601 diabetes mellitus Diseases 0.000 claims description 9
• 238000001727 in vivo Methods 0.000 claims description 9
• 235000021419 vinegar Nutrition 0.000 claims description 9
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
• 229940079593 drug Drugs 0.000 claims description 8
• 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 claims description 8
• 150000002923 oximes Chemical class 0.000 claims description 8
• 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 7
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 7
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
• 230000005764 inhibitory process Effects 0.000 claims description 7
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 7
• 239000000052 vinegar Substances 0.000 claims description 7
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 6
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
• 208000019022 Mood disease Diseases 0.000 claims description 6
• 125000005189 alkyl hydroxy group Chemical group 0.000 claims description 6
• PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 claims description 6
• 230000006999 cognitive decline Effects 0.000 claims description 6
• 150000002148 esters Chemical class 0.000 claims description 6
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 6
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 6
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 6
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 5
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 5
• 241001465754 Metazoa Species 0.000 claims description 5
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 5
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
• 201000011510 cancer Diseases 0.000 claims description 5
• 125000001589 carboacyl group Chemical group 0.000 claims description 5
• 208000035475 disorder Diseases 0.000 claims description 5
• 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
• 208000024714 major depressive disease Diseases 0.000 claims description 5
• 210000002682 neurofibrillary tangle Anatomy 0.000 claims description 5
• 230000036961 partial effect Effects 0.000 claims description 5
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 229910052707 ruthenium Inorganic materials 0.000 claims description 5
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
• UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 claims description 5
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 4
• 208000018737 Parkinson disease Diseases 0.000 claims description 4
• 208000030886 Traumatic Brain injury Diseases 0.000 claims description 4
• 230000007000 age related cognitive decline Effects 0.000 claims description 4
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 4
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
• CVXBEEMKQHEXEN-UHFFFAOYSA-N carbaryl Chemical compound C1=CC=C2C(OC(=O)NC)=CC=CC2=C1 CVXBEEMKQHEXEN-UHFFFAOYSA-N 0.000 claims description 4
• 229960005286 carbaryl Drugs 0.000 claims description 4
• SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 claims description 4
• 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 4
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 230000000694 effects Effects 0.000 claims description 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
• 210000005036 nerve Anatomy 0.000 claims description 4
• 238000006467 substitution reaction Methods 0.000 claims description 4
• 230000009529 traumatic brain injury Effects 0.000 claims description 4
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 3
• 208000017194 Affective disease Diseases 0.000 claims description 3
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 3
• 201000009030 Carcinoma Diseases 0.000 claims description 3
• 201000010374 Down Syndrome Diseases 0.000 claims description 3
• 208000023105 Huntington disease Diseases 0.000 claims description 3
• 206010026749 Mania Diseases 0.000 claims description 3
• 239000004480 active ingredient Substances 0.000 claims description 3
• 230000001919 adrenal effect Effects 0.000 claims description 3
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 3
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims description 3
• 230000007850 degeneration Effects 0.000 claims description 3
• 208000017004 dementia pugilistica Diseases 0.000 claims description 3
• 206010014599 encephalitis Diseases 0.000 claims description 3
• 229910052731 fluorine Inorganic materials 0.000 claims description 3
• 239000011737 fluorine Substances 0.000 claims description 3
• RNIXSZHNJLUJGC-UHFFFAOYSA-N hydroxy(nitro)cyanamide Chemical compound N#CN(O)[N+]([O-])=O RNIXSZHNJLUJGC-UHFFFAOYSA-N 0.000 claims description 3
• 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 3
• 229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
• 235000013336 milk Nutrition 0.000 claims description 3
• 239000008267 milk Substances 0.000 claims description 3
• 210000004080 milk Anatomy 0.000 claims description 3
• 239000011707 mineral Substances 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 125000003386 piperidinyl group Chemical group 0.000 claims description 3
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 2
• 208000000044 Amnesia Diseases 0.000 claims description 2
• 208000031124 Dementia Alzheimer type Diseases 0.000 claims description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
• 201000011240 Frontotemporal dementia Diseases 0.000 claims description 2
• 208000026139 Memory disease Diseases 0.000 claims description 2
• 206010027940 Mood altered Diseases 0.000 claims description 2
• 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 2
• 208000024777 Prion disease Diseases 0.000 claims description 2
• 201000004810 Vascular dementia Diseases 0.000 claims description 2
• 208000028683 bipolar I disease Diseases 0.000 claims description 2
• 208000025307 bipolar depression Diseases 0.000 claims description 2
• 239000003795 chemical substances by application Substances 0.000 claims description 2
• 230000001149 cognitive effect Effects 0.000 claims description 2
• WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 claims description 2
• 230000002996 emotional effect Effects 0.000 claims description 2
• 230000002708 enhancing effect Effects 0.000 claims description 2
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
• 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 description 2
• 229910052747 lanthanoid Inorganic materials 0.000 claims description 2
• 150000002602 lanthanoids Chemical class 0.000 claims description 2
• 238000012423 maintenance Methods 0.000 claims description 2
• 230000006984 memory degeneration Effects 0.000 claims description 2
• 208000023060 memory loss Diseases 0.000 claims description 2
• 230000001575 pathological effect Effects 0.000 claims description 2
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 2
• 230000000750 progressive effect Effects 0.000 claims description 2
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 2
• 235000000346 sugar Nutrition 0.000 claims description 2
• 150000002429 hydrazines Chemical class 0.000 claims 2
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 2
• 241000894007 species Species 0.000 claims 2
• 239000000126 substance Substances 0.000 claims 2
• JJWOMLRJNXMLSO-UHFFFAOYSA-N 1-methylsulfonylpiperidine Chemical compound CS(=O)(=O)N1CCCCC1 JJWOMLRJNXMLSO-UHFFFAOYSA-N 0.000 claims 1
• IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 claims 1
• MJOUJKDTBGXKIU-UHFFFAOYSA-N 4,4-difluoropiperidine Chemical compound FC1(F)CCNCC1 MJOUJKDTBGXKIU-UHFFFAOYSA-N 0.000 claims 1
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 1
• QZLYPMUURJTOOK-UHFFFAOYSA-N NCN(N)NN Chemical compound NCN(N)NN QZLYPMUURJTOOK-UHFFFAOYSA-N 0.000 claims 1
• 206010033799 Paralysis Diseases 0.000 claims 1
• 241000646858 Salix arbusculoides Species 0.000 claims 1
• 241000555745 Sciuridae Species 0.000 claims 1
• UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims 1
• 125000002618 bicyclic heterocycle 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
• 150000007942 carboxylates Chemical class 0.000 claims 1
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 1
• ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims 1
• 238000006073 displacement reaction Methods 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• KIWBPDUYBMNFTB-UHFFFAOYSA-M ethyl sulfate Chemical compound CCOS([O-])(=O)=O KIWBPDUYBMNFTB-UHFFFAOYSA-M 0.000 claims 1
• 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims 1
• 150000002460 imidazoles Chemical class 0.000 claims 1
• 125000002632 imidazolidinyl group Chemical group 0.000 claims 1
• JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 claims 1
• MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
• DIOQZVSQGTUSAI-UHFFFAOYSA-N n-butylhexane Natural products CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims 1
• SZYCWSROMHTCKK-UHFFFAOYSA-N n-ethyl-9h-fluoren-1-amine Chemical compound C1C2=CC=CC=C2C2=C1C(NCC)=CC=C2 SZYCWSROMHTCKK-UHFFFAOYSA-N 0.000 claims 1
• 125000004304 oxazol-5-yl group Chemical group O1C=NC=C1* 0.000 claims 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-O oxonium Chemical compound [OH3+] XLYOFNOQVPJJNP-UHFFFAOYSA-O 0.000 claims 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims 1
• JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims 1
• 239000007921 spray Substances 0.000 claims 1
• 125000004354 sulfur functional group Chemical group 0.000 claims 1
• RSPCKAHMRANGJZ-UHFFFAOYSA-N thiohydroxylamine Chemical compound SN RSPCKAHMRANGJZ-UHFFFAOYSA-N 0.000 claims 1
• 208000014001 urinary system disease Diseases 0.000 claims 1
• 230000008569 process Effects 0.000 abstract description 8
• 238000002360 preparation method Methods 0.000 abstract description 5
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 47
• 238000005481 NMR spectroscopy Methods 0.000 description 45
• 239000000203 mixture Substances 0.000 description 41
• 238000006243 chemical reaction Methods 0.000 description 27
• 235000019439 ethyl acetate Nutrition 0.000 description 27
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 22
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
• 239000003643 water by type Substances 0.000 description 20
• 238000007429 general method Methods 0.000 description 19
• 239000002904 solvent Substances 0.000 description 19
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 13
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
• 239000003112 inhibitor Substances 0.000 description 12
• 229920006395 saturated elastomer Polymers 0.000 description 11
• 239000000543 intermediate Substances 0.000 description 10
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
• 239000011541 reaction mixture Substances 0.000 description 9
• 239000011734 sodium Substances 0.000 description 9
• 238000005160 1H NMR spectroscopy Methods 0.000 description 8
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
• 210000004027 cell Anatomy 0.000 description 8
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