MXPA05006727A

MXPA05006727A - Acidos heteroarilalcanoicos como antagonistas de receptor de integrina.

Acidos heteroarilalcanoicos como antagonistas de receptor de integrina.

Info

Publication number: MXPA05006727A
Authority: MX; Mexico
Prior art keywords: tetrahydro; acid; butanoic; propyl; naphthyridin
Prior art date: 2002-12-20

Application number

MXPA05006727A

Other languages

English (en)

Spanish (es)

Inventor

Bipinchandra N Desai

Original Assignee

Pharmacia Corp

Priority date

2002-12-20

Filing date

2003-12-22

Publication date

2005-09-08

2003-12-22 Application filed by Pharmacia Corp filed Critical Pharmacia Corp

2005-09-08 Publication of MXPA05006727A publication Critical patent/MXPA05006727A/es

Links

239000002253 acid Substances 0.000 title claims description 488
150000007513 acids Chemical class 0.000 title description 2
229940127449 Integrin Receptor Antagonists Drugs 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 143
108010044426 integrins Proteins 0.000 claims abstract description 19
102000006495 integrins Human genes 0.000 claims abstract description 19
150000003839 salts Chemical class 0.000 claims abstract description 17
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
-1 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl Chemical group 0.000 claims description 767
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 204
239000000203 mixture Substances 0.000 claims description 141
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 113
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 79
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 53
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 44
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 39
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 37
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 34
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 21
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
206010028980 Neoplasm Diseases 0.000 claims description 17
125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims description 15
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 14
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 13
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 12
125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 11
230000002265 prevention Effects 0.000 claims description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
206010027476 Metastases Diseases 0.000 claims description 8
230000033115 angiogenesis Effects 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 8
208000002780 macular degeneration Diseases 0.000 claims description 8
230000009401 metastasis Effects 0.000 claims description 8
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
208000001132 Osteoporosis Diseases 0.000 claims description 7
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 7
230000005012 migration Effects 0.000 claims description 7
238000013508 migration Methods 0.000 claims description 7
208000037803 restenosis Diseases 0.000 claims description 7
230000004614 tumor growth Effects 0.000 claims description 7
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
208000017442 Retinal disease Diseases 0.000 claims description 6
206010038923 Retinopathy Diseases 0.000 claims description 6
206010003246 arthritis Diseases 0.000 claims description 6
230000001404 mediated effect Effects 0.000 claims description 6
210000000329 smooth muscle myocyte Anatomy 0.000 claims description 6
SQIIOMYKKDNKJQ-UHFFFAOYSA-N butanoic acid;2,2,2-trifluoroacetic acid Chemical compound CCCC(O)=O.OC(=O)C(F)(F)F SQIIOMYKKDNKJQ-UHFFFAOYSA-N 0.000 claims description 5
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 5
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
241000124008 Mammalia Species 0.000 claims description 4
239000001273 butane Substances 0.000 claims description 4
OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 4
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 3
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
PAAZCQANMCYGAW-UHFFFAOYSA-N acetic acid;2,2,2-trifluoroacetic acid Chemical compound CC(O)=O.OC(=O)C(F)(F)F PAAZCQANMCYGAW-UHFFFAOYSA-N 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
ZCZVGQCBSJLDDS-UHFFFAOYSA-N 1,2,3,4-tetrahydro-1,8-naphthyridine Chemical compound C1=CC=C2CCCNC2=N1 ZCZVGQCBSJLDDS-UHFFFAOYSA-N 0.000 claims description 2
WGSXKYXKAARAKD-UHFFFAOYSA-N 1-fluoro-3-isocyanato-5-(trifluoromethyl)benzene Chemical group FC1=CC(N=C=O)=CC(C(F)(F)F)=C1 WGSXKYXKAARAKD-UHFFFAOYSA-N 0.000 claims description 2
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 2
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 2
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 2
201000001320 Atherosclerosis Diseases 0.000 claims 2
208000037147 Hypercalcaemia Diseases 0.000 claims 2
230000000148 hypercalcaemia Effects 0.000 claims 2
208000030915 hypercalcemia disease Diseases 0.000 claims 2
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
238000000034 method Methods 0.000 abstract description 110
230000002401 inhibitory effect Effects 0.000 abstract description 3
230000003042 antagnostic effect Effects 0.000 abstract description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 339
238000005481 NMR spectroscopy Methods 0.000 description 225
239000000243 solution Substances 0.000 description 174
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 166
239000000047 product Substances 0.000 description 157
235000019439 ethyl acetate Nutrition 0.000 description 129
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 119
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 118
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 116
229910001868 water Inorganic materials 0.000 description 111
229910052739 hydrogen Inorganic materials 0.000 description 109
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 96
239000011541 reaction mixture Substances 0.000 description 96
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 94
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 93
238000006243 chemical reaction Methods 0.000 description 91
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 89
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 81
230000015572 biosynthetic process Effects 0.000 description 80
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 80
238000003786 synthesis reaction Methods 0.000 description 78
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 76
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 71
239000012267 brine Substances 0.000 description 70
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 70
150000003254 radicals Chemical class 0.000 description 69
239000007787 solid Substances 0.000 description 61
239000003921 oil Substances 0.000 description 59
235000019198 oils Nutrition 0.000 description 59
125000000217 alkyl group Chemical group 0.000 description 58
230000002829 reductive effect Effects 0.000 description 53
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 50
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
125000003118 aryl group Chemical group 0.000 description 46
ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 44
239000012044 organic layer Substances 0.000 description 44
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 42
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 36
238000001819 mass spectrum Methods 0.000 description 36
229910052757 nitrogen Inorganic materials 0.000 description 34
238000002360 preparation method Methods 0.000 description 34
239000011734 sodium Substances 0.000 description 34
239000002904 solvent Substances 0.000 description 34
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 34
229920006395 saturated elastomer Polymers 0.000 description 33
239000000741 silica gel Substances 0.000 description 32
229910002027 silica gel Inorganic materials 0.000 description 32
235000019441 ethanol Nutrition 0.000 description 31
125000003545 alkoxy group Chemical group 0.000 description 30
238000003818 flash chromatography Methods 0.000 description 30
238000004458 analytical method Methods 0.000 description 28
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 28
229910052717 sulfur Inorganic materials 0.000 description 28
239000000706 filtrate Substances 0.000 description 27
125000001072 heteroaryl group Chemical group 0.000 description 27
229910052760 oxygen Inorganic materials 0.000 description 27
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
101000873645 Homo sapiens Secretory carrier-associated membrane protein 3 Proteins 0.000 description 26
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
102100035895 Secretory carrier-associated membrane protein 3 Human genes 0.000 description 26
125000001188 haloalkyl group Chemical group 0.000 description 26
125000002887 hydroxy group Chemical group [H]O* 0.000 description 26
238000004007 reversed phase HPLC Methods 0.000 description 26
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 25
229910052938 sodium sulfate Inorganic materials 0.000 description 25
235000011152 sodium sulphate Nutrition 0.000 description 25
238000003756 stirring Methods 0.000 description 25
OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 24
239000003480 eluent Substances 0.000 description 24
239000012043 crude product Substances 0.000 description 22
125000005842 heteroatom Chemical group 0.000 description 22
235000002639 sodium chloride Nutrition 0.000 description 22
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 21
229910052736 halogen Inorganic materials 0.000 description 21
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 21
150000008064 anhydrides Chemical class 0.000 description 20
150000002367 halogens Chemical group 0.000 description 20
125000004432 carbon atom Chemical group C* 0.000 description 19
239000010410 layer Substances 0.000 description 19
239000000377 silicon dioxide Substances 0.000 description 19
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 16
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
125000004429 atom Chemical group 0.000 description 16
238000004128 high performance liquid chromatography Methods 0.000 description 16
239000007832 Na2SO4 Substances 0.000 description 15
239000000284 extract Substances 0.000 description 15
238000010992 reflux Methods 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
229960000583 acetic acid Drugs 0.000 description 14
125000003342 alkenyl group Chemical group 0.000 description 14
125000004183 alkoxy alkyl group Chemical group 0.000 description 14
125000000304 alkynyl group Chemical group 0.000 description 14
239000005557 antagonist Substances 0.000 description 14
125000003710 aryl alkyl group Chemical group 0.000 description 14
239000000460 chlorine Substances 0.000 description 14
238000004587 chromatography analysis Methods 0.000 description 14
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 14
125000000623 heterocyclic group Chemical group 0.000 description 14
125000001424 substituent group Chemical group 0.000 description 14
229910052799 carbon Inorganic materials 0.000 description 13
125000004093 cyano group Chemical group *C#N 0.000 description 13
229910052943 magnesium sulfate Inorganic materials 0.000 description 13
235000019341 magnesium sulphate Nutrition 0.000 description 13
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 12
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
125000002252 acyl group Chemical group 0.000 description 12
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
125000002950 monocyclic group Chemical group 0.000 description 12
239000000843 powder Substances 0.000 description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 12
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 11
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 10
YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
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235000011114 ammonium hydroxide Nutrition 0.000 description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
239000007858 starting material Substances 0.000 description 10
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CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
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OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
125000003282 alkyl amino group Chemical group 0.000 description 9
125000002947 alkylene group Chemical group 0.000 description 9
239000007864 aqueous solution Substances 0.000 description 9
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 9
229940124530 sulfonamide Drugs 0.000 description 9
150000003456 sulfonamides Chemical group 0.000 description 9
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125000002911 monocyclic heterocycle group Chemical group 0.000 description 8
239000012299 nitrogen atmosphere Substances 0.000 description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
229910000104 sodium hydride Inorganic materials 0.000 description 8
125000004001 thioalkyl group Chemical group 0.000 description 8
OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 7
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125000002619 bicyclic group Chemical group 0.000 description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
125000004181 carboxyalkyl group Chemical group 0.000 description 7
239000012230 colorless oil Substances 0.000 description 7
239000001257 hydrogen Substances 0.000 description 7
125000002768 hydroxyalkyl group Chemical group 0.000 description 7
125000004433 nitrogen atom Chemical group N* 0.000 description 7
239000001301 oxygen Substances 0.000 description 7
229910052763 palladium Inorganic materials 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
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WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
239000004215 Carbon black (E152) Substances 0.000 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
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WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 6
125000004442 acylamino group Chemical group 0.000 description 6
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
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