ES2365258T3 - Derivados de tiazol condensados como inhibidores de quinasa. - Google Patents

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Publication number

ES2365258T3

ES2365258T3 ES07733382T ES07733382T ES2365258T3 ES 2365258 T3 ES2365258 T3 ES 2365258T3 ES 07733382 T ES07733382 T ES 07733382T ES 07733382 T ES07733382 T ES 07733382T ES 2365258 T3 ES2365258 T3 ES 2365258T3

Authority

ES

Spain

Prior art keywords

alkyl

amino

dialkyl

pyrazolyl

pyridinyl

Prior art date

2006-06-26

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.)

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• 239000003112 inhibitor Substances 0.000 title description 5
• 238000011282 treatment Methods 0.000 claims abstract description 67
• 230000002757 inflammatory effect Effects 0.000 claims abstract description 6
• 230000001363 autoimmune Effects 0.000 claims abstract description 5
• 230000002503 metabolic effect Effects 0.000 claims abstract description 5
• 230000000626 neurodegenerative effect Effects 0.000 claims abstract description 5
• 230000003040 nociceptive effect Effects 0.000 claims abstract description 5
• 230000000771 oncological effect Effects 0.000 claims abstract description 5
• 229940124639 Selective inhibitor Drugs 0.000 claims abstract description 4
• 239000003814 drug Substances 0.000 claims abstract description 4
• 230000002526 effect on cardiovascular system Effects 0.000 claims abstract description 3
• -1 haloarylpyrrolidinyl Chemical group 0.000 claims description 1893
• 125000000217 alkyl group Chemical group 0.000 claims description 556
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 352
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 322
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 282
• 150000001875 compounds Chemical class 0.000 claims description 233
• 125000004076 pyridyl group Chemical group 0.000 claims description 177
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 175
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 157
• 125000003118 aryl group Chemical group 0.000 claims description 133
• 125000003545 alkoxy group Chemical group 0.000 claims description 112
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 111
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 93
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 92
• 229910052739 hydrogen Inorganic materials 0.000 claims description 90
• 239000001257 hydrogen Substances 0.000 claims description 90
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 80
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 79
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 63
• 125000001424 substituent group Chemical group 0.000 claims description 58
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 51
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 49
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 48
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 47
• 229910052736 halogen Inorganic materials 0.000 claims description 45
• 150000002367 halogens Chemical class 0.000 claims description 44
• 125000004990 dihydroxyalkyl group Chemical group 0.000 claims description 42
• 125000001072 heteroaryl group Chemical group 0.000 claims description 41
• 150000002431 hydrogen Chemical class 0.000 claims description 41
• 125000002757 morpholinyl group Chemical group 0.000 claims description 39
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 38
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 36
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 35
• 125000003386 piperidinyl group Chemical group 0.000 claims description 33
• 229910052799 carbon Inorganic materials 0.000 claims description 32
• 150000003839 salts Chemical class 0.000 claims description 32
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 27
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 27
• 125000002883 imidazolyl group Chemical group 0.000 claims description 26
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 26
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 25
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 25
• 239000012453 solvate Substances 0.000 claims description 24
• 125000004104 aryloxy group Chemical group 0.000 claims description 23
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 23
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 22
• 125000000335 thiazolyl group Chemical group 0.000 claims description 22
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 22
• 125000003342 alkenyl group Chemical group 0.000 claims description 21
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 21
• 125000006542 morpholinylalkyl group Chemical group 0.000 claims description 21
• 150000001721 carbon Chemical group 0.000 claims description 20
• 125000004193 piperazinyl group Chemical group 0.000 claims description 20
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 18
• 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 18
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 17
• 125000004432 carbon atom Chemical group C* 0.000 claims description 17
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 16
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 16
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 16
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 16
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 15
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 15
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
• 125000000304 alkynyl group Chemical group 0.000 claims description 14
• 125000001425 triazolyl group Chemical group 0.000 claims description 14
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 13
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 13
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
• 125000005243 carbonyl alkyl group Chemical group 0.000 claims description 11
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 11
• 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 10
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 10
• 125000002393 azetidinyl group Chemical group 0.000 claims description 10
• 125000001041 indolyl group Chemical group 0.000 claims description 10
• 229910052757 nitrogen Inorganic materials 0.000 claims description 10
• 150000002923 oximes Chemical class 0.000 claims description 10
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 8
• 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 8
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 8
• 125000005159 cyanoalkoxy group Chemical group 0.000 claims description 8
• 125000003106 haloaryl group Chemical group 0.000 claims description 8
• 125000004996 haloaryloxy group Chemical group 0.000 claims description 8
• 125000005968 oxazolinyl group Chemical group 0.000 claims description 8
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 7
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 7
• 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 7
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 7
• 125000004414 alkyl thio group Chemical group 0.000 claims description 7
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 7
• 125000005222 heteroarylaminocarbonyl group Chemical group 0.000 claims description 7
• 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 7
• 125000004750 (C1-C6) alkylaminosulfonyl group Chemical group 0.000 claims description 6
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 6
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
• 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 5
• 201000010099 disease Diseases 0.000 claims description 5
• 239000001301 oxygen Substances 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 230000002265 prevention Effects 0.000 claims description 5
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 5
• 125000001544 thienyl group Chemical group 0.000 claims description 5
• 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 4
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
• 101100294104 Caenorhabditis elegans nhr-34 gene Proteins 0.000 claims description 3
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
• 229910052717 sulfur Chemical group 0.000 claims description 3
• 239000011593 sulfur Chemical group 0.000 claims description 3
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
• 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 2
• 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 2
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 2
• 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 claims description 2
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 2
• 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 claims description 2
• 125000004987 dibenzofuryl group Chemical group C1(=CC=CC=2OC3=C(C21)C=CC=C3)* 0.000 claims description 2
• 125000002541 furyl group Chemical group 0.000 claims description 2
• 125000000623 heterocyclic group Chemical group 0.000 claims description 2
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims description 2
• 125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
• 125000002971 oxazolyl group Chemical group 0.000 claims description 2
• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
• 125000001984 thiazolidinyl group Chemical group 0.000 claims description 2
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims 30
• 125000005129 aryl carbonyl group Chemical group 0.000 claims 5
• 125000003282 alkyl amino group Chemical group 0.000 claims 4
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 3
• 125000005016 hydroxyalkynyl group Chemical group 0.000 claims 3
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 2
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 2
• 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims 2
• 241001024304 Mino Species 0.000 claims 1
• CHVAWSWMXBIOLB-UHFFFAOYSA-N n-phenyl-1,3-oxazol-2-amine Chemical compound C=1C=CC=CC=1NC1=NC=CO1 CHVAWSWMXBIOLB-UHFFFAOYSA-N 0.000 claims 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 abstract description 5
• QGUSXKFSPVAZOB-UHFFFAOYSA-N 6,7-dihydro-5h-[1,3]thiazolo[5,4-c]pyridin-4-one Chemical class O=C1NCCC2=C1SC=N2 QGUSXKFSPVAZOB-UHFFFAOYSA-N 0.000 abstract description 2
• 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 abstract 1
• 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 abstract 1
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 68
• 125000005843 halogen group Chemical group 0.000 description 59
• 238000000034 method Methods 0.000 description 55
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
• 239000012071 phase Substances 0.000 description 40
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
• 239000000243 solution Substances 0.000 description 37
• 239000011541 reaction mixture Substances 0.000 description 35
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 33
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 31
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 30
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 29
• 229910052794 bromium Inorganic materials 0.000 description 29
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 28
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 27
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 25
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 22
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 22
• 239000002904 solvent Substances 0.000 description 22
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
• 125000006301 indolyl methyl group Chemical group 0.000 description 20
• 239000000203 mixture Substances 0.000 description 20
• 239000007787 solid Substances 0.000 description 20
• 238000000746 purification Methods 0.000 description 19
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 18
• 239000002585 base Substances 0.000 description 18
• 238000006243 chemical reaction Methods 0.000 description 18
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 17
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 16
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
• 239000003054 catalyst Substances 0.000 description 16
• 125000001153 fluoro group Chemical group F* 0.000 description 16
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 16
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 16
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 15
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• 125000005605 benzo group Chemical group 0.000 description 15
• 125000001309 chloro group Chemical group Cl* 0.000 description 15
• 235000019253 formic acid Nutrition 0.000 description 15
• 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 15
• 235000019439 ethyl acetate Nutrition 0.000 description 14
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 13
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
• 230000008569 process Effects 0.000 description 12
• 125000003944 tolyl group Chemical group 0.000 description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
• 239000002253 acid Substances 0.000 description 11
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
• 239000003921 oil Substances 0.000 description 11
• 235000019198 oils Nutrition 0.000 description 11
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
• 125000000638 benzylaminocarbonyl group Chemical group C(C1=CC=CC=C1)NC(=O)* 0.000 description 10
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
• 238000002360 preparation method Methods 0.000 description 10
• 239000000377 silicon dioxide Substances 0.000 description 10
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 150000001412 amines Chemical class 0.000 description 9
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 9
• 125000006263 dimethyl aminosulfonyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])S(*)(=O)=O 0.000 description 9
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 9
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
• 235000019341 magnesium sulphate Nutrition 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• 125000006278 bromobenzyl group Chemical group 0.000 description 8
• 239000000460 chlorine Substances 0.000 description 8
• 229910052801 chlorine Inorganic materials 0.000 description 8
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 8
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 8
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 7
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 7
• 235000011114 ammonium hydroxide Nutrition 0.000 description 7
• 239000012267 brine Substances 0.000 description 7
• 229910052681 coesite Inorganic materials 0.000 description 7
• 229910052906 cristobalite Inorganic materials 0.000 description 7
• 239000000543 intermediate Substances 0.000 description 7
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 7
• 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 7
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 7
• 235000012239 silicon dioxide Nutrition 0.000 description 7
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
• 229910052682 stishovite Inorganic materials 0.000 description 7
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