SK2142003A3 - Quinazoline derivatives, process for their preparation, pharmaceutical composition comprising same and their use - Google Patents

Info

Publication number

SK2142003A3

SK2142003A3 SK214-2003A SK2142003A SK2142003A3 SK 2142003 A3 SK2142003 A3 SK 2142003A3 SK 2142003 A SK2142003 A SK 2142003A SK 2142003 A3 SK2142003 A3 SK 2142003A3

Authority

SK

Slovakia

Prior art keywords

group

carbon atoms

ethoxy

propoxy

alkyl

Prior art date

2000-08-21

Links

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• Global Dossier
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• 238000000034 method Methods 0.000 title claims abstract description 59
• 238000002360 preparation method Methods 0.000 title claims abstract description 41
• 230000008569 process Effects 0.000 title claims abstract description 9
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 5
• 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title abstract description 6
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 32
• 239000003795 chemical substances by application Substances 0.000 claims abstract description 9
• 239000003814 drug Substances 0.000 claims abstract description 9
• 230000001740 anti-invasion Effects 0.000 claims abstract description 8
• -1 nitro, hydroxy , mercapto, amino, formyl Chemical group 0.000 claims description 806
• 125000004432 carbon atom Chemical group C* 0.000 claims description 281
• 125000000217 alkyl group Chemical group 0.000 claims description 173
• 125000001424 substituent group Chemical group 0.000 claims description 116
• 150000001875 compounds Chemical class 0.000 claims description 111
• 150000003246 quinazolines Chemical class 0.000 claims description 60
• 239000001257 hydrogen Substances 0.000 claims description 58
• 229910052739 hydrogen Inorganic materials 0.000 claims description 58
• 150000003839 salts Chemical class 0.000 claims description 58
• 125000000623 heterocyclic group Chemical group 0.000 claims description 50
• 229910052757 nitrogen Inorganic materials 0.000 claims description 45
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 42
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 36
• 238000006243 chemical reaction Methods 0.000 claims description 34
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 34
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 32
• 125000003545 alkoxy group Chemical group 0.000 claims description 31
• 229910052801 chlorine Inorganic materials 0.000 claims description 29
• 229910052760 oxygen Inorganic materials 0.000 claims description 29
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 29
• 125000001072 heteroaryl group Chemical group 0.000 claims description 27
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
• 239000002253 acid Substances 0.000 claims description 25
• 229910052731 fluorine Inorganic materials 0.000 claims description 24
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 23
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
• 125000006239 protecting group Chemical group 0.000 claims description 21
• 125000003118 aryl group Chemical group 0.000 claims description 20
• 229910052799 carbon Inorganic materials 0.000 claims description 20
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 19
• 229910052736 halogen Inorganic materials 0.000 claims description 19
• 150000002367 halogens Chemical class 0.000 claims description 19
• 239000000460 chlorine Substances 0.000 claims description 18
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 18
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 16
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 16
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 15
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 14
• 241000282414 Homo sapiens Species 0.000 claims description 14
• 125000002947 alkylene group Chemical group 0.000 claims description 14
• 239000011737 fluorine Substances 0.000 claims description 14
• 241001465754 Metazoa Species 0.000 claims description 13
• 125000003342 alkenyl group Chemical group 0.000 claims description 13
• 125000001589 carboacyl group Chemical group 0.000 claims description 13
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 13
• 238000003776 cleavage reaction Methods 0.000 claims description 13
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 13
• 238000003780 insertion Methods 0.000 claims description 13
• 230000037431 insertion Effects 0.000 claims description 13
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 12
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
• 230000007017 scission Effects 0.000 claims description 12
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 11
• 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 11
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 11
• 229910052717 sulfur Inorganic materials 0.000 claims description 11
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 10
• 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 10
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 10
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 10
• 125000001153 fluoro group Chemical group F* 0.000 claims description 10
• 125000004435 hydrogen atom Chemical group [H]* 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
• 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 10
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 9
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 9
• 125000004423 acyloxy group Chemical group 0.000 claims description 9
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 9
• 125000000304 alkynyl group Chemical group 0.000 claims description 9
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 9
• 125000004429 atom Chemical group 0.000 claims description 9
• 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 9
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 9
• 125000005843 halogen group Chemical group 0.000 claims description 9
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 9
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
• 125000003282 alkyl amino group Chemical group 0.000 claims description 8
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 8
• 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 8
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 8
• 150000003852 triazoles Chemical group 0.000 claims description 8
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 7
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 7
• 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 7
• 125000006766 (C2-C6) alkynyloxy group Chemical group 0.000 claims description 7
• 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 7
• 150000001412 amines Chemical class 0.000 claims description 7
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 7
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 7
• 229920002554 vinyl polymer Polymers 0.000 claims description 7
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 6
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 6
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 6
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
• 125000004076 pyridyl group Chemical group 0.000 claims description 6
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 5
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 5
• 125000000524 functional group Chemical group 0.000 claims description 5
• 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 5
• 125000001425 triazolyl group Chemical group 0.000 claims description 5
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 4
• XHOHVIKZCDXJNK-UHFFFAOYSA-N 2-piperazin-1-ylacetonitrile Chemical compound N#CCN1CCNCC1 XHOHVIKZCDXJNK-UHFFFAOYSA-N 0.000 claims description 4
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 4
• 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 4
• 125000003277 amino group Chemical group 0.000 claims description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• 238000002560 therapeutic procedure Methods 0.000 claims description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
• 150000001721 carbon Chemical group 0.000 claims description 3
• 239000012024 dehydrating agents‎ Substances 0.000 claims description 3
• 125000001188 haloalkyl group Chemical group 0.000 claims description 3
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
• MWCIFBSDQJFWIE-UHFFFAOYSA-N n-(5-bromo-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C(=CC=C4OCOC4=3)Br)N=CN=C2C=C1OCCCN1CCCCC1 MWCIFBSDQJFWIE-UHFFFAOYSA-N 0.000 claims description 3
• 239000001301 oxygen Substances 0.000 claims description 3
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
• FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 2
• GDKVKFPZULERFV-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-4-ylamino)-6-methoxyquinazolin-7-yl]oxy-3-pyrrolidin-1-ylpropan-2-ol Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCC(O)CN1CCCC1 GDKVKFPZULERFV-UHFFFAOYSA-N 0.000 claims description 2
• QTDVHHYSYHHNBA-UHFFFAOYSA-N 2-[4-[3-[4-[(5-chloro-1,3-benzodioxol-4-yl)amino]-6-methoxyquinazolin-7-yl]oxypropyl]piperazin-1-yl]acetonitrile Chemical compound COC1=CC2=C(NC=3C(=CC=C4OCOC4=3)Cl)N=CN=C2C=C1OCCCN1CCN(CC#N)CC1 QTDVHHYSYHHNBA-UHFFFAOYSA-N 0.000 claims description 2
• DLSRIJJGQIAZHW-UHFFFAOYSA-N 4-[[4-[(5-chloro-1,3-benzodioxol-4-yl)amino]-6-methoxyquinazolin-7-yl]oxymethyl]pyridine-2-carbonitrile Chemical compound COC1=CC2=C(NC=3C(=CC=C4OCOC4=3)Cl)N=CN=C2C=C1OCC1=CC=NC(C#N)=C1 DLSRIJJGQIAZHW-UHFFFAOYSA-N 0.000 claims description 2
• 230000029936 alkylation Effects 0.000 claims description 2
• 238000005804 alkylation reaction Methods 0.000 claims description 2
• 125000001246 bromo group Chemical group Br* 0.000 claims description 2
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• DNWPHHNJIJAHJZ-UHFFFAOYSA-N n-(1,3-benzodioxol-4-yl)-6-methoxy-7-(2-pyridin-4-yloxyethoxy)quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCCOC1=CC=NC=C1 DNWPHHNJIJAHJZ-UHFFFAOYSA-N 0.000 claims description 2
• FQYJMIYZRDNWFL-UHFFFAOYSA-N n-(1,3-benzodioxol-4-yl)-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCCCN1CCCCC1 FQYJMIYZRDNWFL-UHFFFAOYSA-N 0.000 claims description 2
• QGPNNNIDDPCLOP-UHFFFAOYSA-N n-(1,3-benzodioxol-4-yl)-6-methoxy-7-(pyridin-3-ylmethoxy)quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCC1=CC=CN=C1 QGPNNNIDDPCLOP-UHFFFAOYSA-N 0.000 claims description 2
• RMCMKWWPSMSMQU-UHFFFAOYSA-N n-(1,3-benzodioxol-4-yl)-6-methoxy-7-[2-(4-methylpiperazin-1-yl)ethoxy]quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCCN1CCN(C)CC1 RMCMKWWPSMSMQU-UHFFFAOYSA-N 0.000 claims description 2
• WACGGXLWSGDPHZ-UHFFFAOYSA-N n-(1,3-benzodioxol-4-yl)-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCCCN1CCN(C)CC1 WACGGXLWSGDPHZ-UHFFFAOYSA-N 0.000 claims description 2
• ULKTVLPBTPXRFB-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C(=CC=C4OCOC4=3)Cl)N=CN=C2C=C1OCCCN1CCCC1 ULKTVLPBTPXRFB-UHFFFAOYSA-N 0.000 claims description 2
• UYKYCBACTCRLLP-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C(=CC=C4OCOC4=3)Cl)N=CN=C2C=C1OCC1CCN(C)CC1 UYKYCBACTCRLLP-UHFFFAOYSA-N 0.000 claims description 2
• 125000004043 oxo group Chemical group O=* 0.000 claims description 2
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 2
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 2
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims 2
• QCEYSUFQHXTGTC-UHFFFAOYSA-N 1-[4-(1,3-benzodioxol-4-ylamino)-6-methoxyquinazolin-7-yl]oxy-3-[methyl(propan-2-yl)amino]propan-2-ol Chemical compound N1=CN=C2C=C(OCC(O)CN(C)C(C)C)C(OC)=CC2=C1NC1=CC=CC2=C1OCO2 QCEYSUFQHXTGTC-UHFFFAOYSA-N 0.000 claims 1
• VJXBEBMWTIRUQU-UHFFFAOYSA-N 2-[4-[3-[4-(1,3-benzodioxol-4-ylamino)-6-methoxyquinazolin-7-yl]oxy-2-hydroxypropyl]piperazin-1-yl]acetonitrile Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCC(O)CN1CCN(CC#N)CC1 VJXBEBMWTIRUQU-UHFFFAOYSA-N 0.000 claims 1
• 235000007119 Ananas comosus Nutrition 0.000 claims 1
• 244000099147 Ananas comosus Species 0.000 claims 1
• AYVXLBYVMHZUFF-UHFFFAOYSA-N COC(C(=O)NC(C(=O)N(OCCCC)OC(C)C)(C(N(C)C)(NCC)NC)N(CC)CC)(OCCC)OCC Chemical compound COC(C(=O)NC(C(=O)N(OCCCC)OC(C)C)(C(N(C)C)(NCC)NC)N(CC)CC)(OCCC)OCC AYVXLBYVMHZUFF-UHFFFAOYSA-N 0.000 claims 1
• 125000005117 dialkylcarbamoyl group Chemical group 0.000 claims 1
• 125000004438 haloalkoxy group Chemical group 0.000 claims 1
• JANJZCFEDLKWOM-UHFFFAOYSA-N n-(1,3-benzodioxol-4-yl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCC1CCN(C)CC1 JANJZCFEDLKWOM-UHFFFAOYSA-N 0.000 claims 1
• IFKVYXZTVIFTQM-UHFFFAOYSA-N n-(1,3-benzodioxol-4-yl)-6-methoxy-7-[2-(1-methylpiperidin-4-yl)ethoxy]quinazolin-4-amine Chemical compound COC1=CC2=C(NC=3C=4OCOC=4C=CC=3)N=CN=C2C=C1OCCC1CCN(C)CC1 IFKVYXZTVIFTQM-UHFFFAOYSA-N 0.000 claims 1
• 125000003386 piperidinyl group Chemical group 0.000 claims 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
• 238000004519 manufacturing process Methods 0.000 abstract description 2
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 342
• 239000000203 mixture Substances 0.000 description 288
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 251
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 168
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 165
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 147
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 130
• 238000001819 mass spectrum Methods 0.000 description 116
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 114
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 109
• 239000000243 solution Substances 0.000 description 107
• 150000002431 hydrogen Chemical class 0.000 description 100
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 98
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 96
• 239000007787 solid Substances 0.000 description 73
• 239000007858 starting material Substances 0.000 description 69
• 239000000047 product Substances 0.000 description 68
• 239000000463 material Substances 0.000 description 66
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 62
• 238000004440 column chromatography Methods 0.000 description 56
• 239000000377 silicon dioxide Substances 0.000 description 52
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 49
• 235000019341 magnesium sulphate Nutrition 0.000 description 49
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 48
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
• 239000011541 reaction mixture Substances 0.000 description 48
• 238000001914 filtration Methods 0.000 description 47
• 239000012267 brine Substances 0.000 description 45
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 45
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 43
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 41
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 38
• DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 38
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 31
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 31
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 30
• 239000012074 organic phase Substances 0.000 description 30
• 238000005481 NMR spectroscopy Methods 0.000 description 29
• 102000001332 SRC Human genes 0.000 description 29
• 108060006706 SRC Proteins 0.000 description 29
• 239000000706 filtrate Substances 0.000 description 28
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
• 210000004027 cell Anatomy 0.000 description 27
• 229920006395 saturated elastomer Polymers 0.000 description 26
• 238000012360 testing method Methods 0.000 description 26
• 235000017557 sodium bicarbonate Nutrition 0.000 description 23
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