AU2008251692B2 - P70 S6 kinase inhibitors - Google Patents

Info

Publication number

AU2008251692B2

AU2008251692B2 AU2008251692A AU2008251692A AU2008251692B2 AU 2008251692 B2 AU2008251692 B2 AU 2008251692B2 AU 2008251692 A AU2008251692 A AU 2008251692A AU 2008251692 A AU2008251692 A AU 2008251692A AU 2008251692 B2 AU2008251692 B2 AU 2008251692B2

Authority

AU

Australia

Prior art keywords

phenyl

imidazol

trifluoromethyl

compound

piperidine

Prior art date

2007-05-11

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.)

Ceased

Links

• Espacenet
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• 108010013238 70-kDa Ribosomal Protein S6 Kinases Proteins 0.000 title abstract description 21
• 229940043355 kinase inhibitor Drugs 0.000 title abstract description 6
• 239000003757 phosphotransferase inhibitor Substances 0.000 title abstract description 6
• 238000000034 method Methods 0.000 claims abstract description 35
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
• 150000001875 compounds Chemical class 0.000 claims description 244
• 150000003839 salts Chemical class 0.000 claims description 74
• 241000124008 Mammalia Species 0.000 claims description 44
• 239000003814 drug Substances 0.000 claims description 21
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 18
• 238000004519 manufacturing process Methods 0.000 claims description 17
• 239000003085 diluting agent Substances 0.000 claims description 15
• 239000003937 drug carrier Substances 0.000 claims description 13
• 208000009956 adenocarcinoma Diseases 0.000 claims description 10
• 210000001072 colon Anatomy 0.000 claims description 10
• 230000033115 angiogenesis Effects 0.000 claims description 9
• 230000005764 inhibitory process Effects 0.000 claims description 9
• 230000002401 inhibitory effect Effects 0.000 claims description 6
• 230000014399 negative regulation of angiogenesis Effects 0.000 claims description 6
• HDYUXDNMHBQKAU-UHFFFAOYSA-N 4-[4-[4-[4-fluoro-3-(trifluoromethyl)phenyl]-1-methylimidazol-2-yl]piperidin-1-yl]-1h-pyrazolo[3,4-d]pyrimidine;4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.N1=C(C2CCN(CC2)C=2C=3C=NNC=3N=CN=2)N(C)C=C1C1=CC=C(F)C(C(F)(F)F)=C1 HDYUXDNMHBQKAU-UHFFFAOYSA-N 0.000 claims description 5
• 238000002560 therapeutic procedure Methods 0.000 claims description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 193
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 156
• 238000002360 preparation method Methods 0.000 description 136
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 135
• 239000000203 mixture Substances 0.000 description 89
• 238000003756 stirring Methods 0.000 description 88
• 239000007787 solid Substances 0.000 description 80
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 79
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 78
• 238000006243 chemical reaction Methods 0.000 description 72
• 239000000243 solution Substances 0.000 description 71
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 69
• 239000012141 concentrate Substances 0.000 description 67
• 235000008504 concentrate Nutrition 0.000 description 67
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 64
• 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 64
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 63
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 56
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
• 235000019439 ethyl acetate Nutrition 0.000 description 52
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 50
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 46
• 229920006395 saturated elastomer Polymers 0.000 description 38
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 36
• 239000011780 sodium chloride Substances 0.000 description 34
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
• 239000002904 solvent Substances 0.000 description 31
• 125000005843 halogen group Chemical group 0.000 description 30
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 29
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
• 239000012044 organic layer Substances 0.000 description 29
• 125000001424 substituent group Chemical group 0.000 description 29
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 28
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
• 239000002002 slurry Substances 0.000 description 25
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 24
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 23
• -1 for example Chemical group 0.000 description 23
• 239000011734 sodium Substances 0.000 description 23
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 21
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
• 239000000460 chlorine Substances 0.000 description 19
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 19
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 19
• 239000000047 product Substances 0.000 description 19
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
• 239000000741 silica gel Substances 0.000 description 17
• 229910002027 silica gel Inorganic materials 0.000 description 17
• RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 16
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 16
• 239000011541 reaction mixture Substances 0.000 description 15
• 210000004027 cell Anatomy 0.000 description 14
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 14
• 229910052757 nitrogen Inorganic materials 0.000 description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 14
• DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 14
• 238000010898 silica gel chromatography Methods 0.000 description 14
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 13
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 13
• NFEZOYIKZXDOAJ-UHFFFAOYSA-N 2,4-bis(trifluoromethyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine;hydrochloride Chemical compound Cl.C1NCCC2=C1N=C(C(F)(F)F)N=C2C(F)(F)F NFEZOYIKZXDOAJ-UHFFFAOYSA-N 0.000 description 12
• 239000000284 extract Substances 0.000 description 12
• 239000000706 filtrate Substances 0.000 description 12
• 229910052739 hydrogen Inorganic materials 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
• 206010028980 Neoplasm Diseases 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
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
• 239000003921 oil Substances 0.000 description 10
• 235000019198 oils Nutrition 0.000 description 10
• 238000010992 reflux Methods 0.000 description 10
• YMXQUFUYCADCFL-UHFFFAOYSA-N 4-chloro-1h-pyrazolo[3,4-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=NN2 YMXQUFUYCADCFL-UHFFFAOYSA-N 0.000 description 9
• 239000001257 hydrogen Substances 0.000 description 9
• 239000010410 layer Substances 0.000 description 9
• PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
• 150000001409 amidines Chemical class 0.000 description 8
• 238000004587 chromatography analysis Methods 0.000 description 8
• 238000001816 cooling Methods 0.000 description 8
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 8
• HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 8
• 239000003981 vehicle Substances 0.000 description 8
• JWOHBPPVVDQMKB-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC(C(O)=O)CC1 JWOHBPPVVDQMKB-UHFFFAOYSA-N 0.000 description 7
• 206010049459 Lymphangioleiomyomatosis Diseases 0.000 description 7
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
• 238000005481 NMR spectroscopy Methods 0.000 description 7
• 229960000583 acetic acid Drugs 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 239000012458 free base Substances 0.000 description 7
• 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 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 7
• ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-UHFFFAOYSA-N 0.000 description 6
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 6
• 239000005695 Ammonium acetate Substances 0.000 description 6
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 238000002441 X-ray diffraction Methods 0.000 description 6
• 229940043376 ammonium acetate Drugs 0.000 description 6
• 235000019257 ammonium acetate Nutrition 0.000 description 6
• 239000002585 base Substances 0.000 description 6
• 230000000694 effects Effects 0.000 description 6
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
• 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 6
• NRWQPBZQKWFIIY-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine;dihydrochloride Chemical compound Cl.Cl.C1=NC=C2C=NNC2=N1 NRWQPBZQKWFIIY-UHFFFAOYSA-N 0.000 description 5
• HIZQPRUZZYAVRY-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine;hydrochloride Chemical compound Cl.C1=NC=C2C=NNC2=N1 HIZQPRUZZYAVRY-UHFFFAOYSA-N 0.000 description 5
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
• 201000010915 Glioblastoma multiforme Diseases 0.000 description 5
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• 208000005017 glioblastoma Diseases 0.000 description 5
• VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 5
• DRGCXLJWMQGVJA-UHFFFAOYSA-N pyrimidine;dihydrochloride Chemical compound Cl.Cl.C1=CN=CN=C1 DRGCXLJWMQGVJA-UHFFFAOYSA-N 0.000 description 5
• 239000000523 sample Substances 0.000 description 5
• 229910052938 sodium sulfate Inorganic materials 0.000 description 5
• 235000011152 sodium sulphate Nutrition 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• NOGILORWSQYUJQ-UHFFFAOYSA-N tert-butyl 4-[[2-oxo-2-[3-(trifluoromethyl)phenyl]ethyl]carbamoyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(=O)NCC(=O)C1=CC=CC(C(F)(F)F)=C1 NOGILORWSQYUJQ-UHFFFAOYSA-N 0.000 description 5
• 238000005406 washing Methods 0.000 description 5
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical compound C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 description 4
• TZIYNLSEBAYCBZ-UHFFFAOYSA-N 2-bromo-1-[3-(trifluoromethyl)phenyl]ethanone Chemical compound FC(F)(F)C1=CC=CC(C(=O)CBr)=C1 TZIYNLSEBAYCBZ-UHFFFAOYSA-N 0.000 description 4
• FYXRSVDHGLUMHB-UHFFFAOYSA-N 4-[4-[4-[4-fluoro-3-(trifluoromethyl)phenyl]-1-methylimidazol-2-yl]piperidin-1-yl]-1h-pyrazolo[3,4-d]pyrimidine Chemical compound N1=C(C2CCN(CC2)C=2C=3C=NNC=3N=CN=2)N(C)C=C1C1=CC=C(F)C(C(F)(F)F)=C1 FYXRSVDHGLUMHB-UHFFFAOYSA-N 0.000 description 4
• RSFBRAHCHZGZPB-UHFFFAOYSA-N 4-[4-[5-[3-(trifluoromethyl)phenyl]-1h-imidazol-2-yl]piperidin-1-yl]-1h-pyrazolo[3,4-d]pyrimidine Chemical compound FC(F)(F)C1=CC=CC(C=2N=C(NC=2)C2CCN(CC2)C=2C=3C=NNC=3N=CN=2)=C1 RSFBRAHCHZGZPB-UHFFFAOYSA-N 0.000 description 4
• ROGYJTCGEPAVSF-UHFFFAOYSA-N 4-[5-[3-(trifluoromethyl)phenyl]-1h-imidazol-2-yl]piperidine Chemical compound FC(F)(F)C1=CC=CC(C=2N=C(NC=2)C2CCNCC2)=C1 ROGYJTCGEPAVSF-UHFFFAOYSA-N 0.000 description 4
• JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 4
• DLCWBLXVWDWBEM-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine;hydrochloride Chemical compound Cl.N1=CNC2=NC=CC2=C1 DLCWBLXVWDWBEM-UHFFFAOYSA-N 0.000 description 4
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 4
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• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
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• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
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• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
• WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 4
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• 125000003545 alkoxy group Chemical group 0.000 description 4
• 125000000217 alkyl group Chemical group 0.000 description 4
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• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
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• 150000007942 carboxylates Chemical class 0.000 description 4
• 238000004440 column chromatography Methods 0.000 description 4
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• 125000000753 cycloalkyl group Chemical group 0.000 description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
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• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 239000000377 silicon dioxide Substances 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
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• 239000012312 sodium hydride Substances 0.000 description 4
• 229910000104 sodium hydride Inorganic materials 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
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