JP6353772B2 - 2−アルコキシ−5−(トリフルオロメチル)ピリミジン誘導体及びその製造方法 - Google Patents
2−アルコキシ−5−(トリフルオロメチル)ピリミジン誘導体及びその製造方法 Download PDFInfo
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- JP6353772B2 JP6353772B2 JP2014237928A JP2014237928A JP6353772B2 JP 6353772 B2 JP6353772 B2 JP 6353772B2 JP 2014237928 A JP2014237928 A JP 2014237928A JP 2014237928 A JP2014237928 A JP 2014237928A JP 6353772 B2 JP6353772 B2 JP 6353772B2
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- JP
- Japan
- Prior art keywords
- pyrimidine
- trifluoromethyl
- methyl
- amino
- butoxy
- Prior art date
- 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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- 238000004519 manufacturing process Methods 0.000 title claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 229910052751 metal Inorganic materials 0.000 claims description 11
- 239000002184 metal Substances 0.000 claims description 11
- BQDJLAWUTBCDHK-UHFFFAOYSA-N 2-(trifluoromethyl)pyrimidine Chemical class FC(F)(F)C1=NC=CC=N1 BQDJLAWUTBCDHK-UHFFFAOYSA-N 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- GPNLIJCOIGHUQD-UHFFFAOYSA-N 2-phenylmethoxy-5-(trifluoromethyl)pyrimidine Chemical class C(C1=CC=CC=C1)OC1=NC=C(C=N1)C(F)(F)F GPNLIJCOIGHUQD-UHFFFAOYSA-N 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 150000004703 alkoxides Chemical class 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 445
- -1 substituted-5- (trifluoromethyl) pyrimidine Chemical class 0.000 description 332
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 45
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 239000012043 crude product Substances 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 21
- ZQBFAOFFOQMSGJ-UHFFFAOYSA-N hexafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1F ZQBFAOFFOQMSGJ-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
- AVTHDZMBGIZIPD-UHFFFAOYSA-N COC1=NC=C(C(=N1)N(C)C1=CC=CC=C1)C(F)(F)F Chemical compound COC1=NC=C(C(=N1)N(C)C1=CC=CC=C1)C(F)(F)F AVTHDZMBGIZIPD-UHFFFAOYSA-N 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 12
- SUHGANDNTPOCSQ-UHFFFAOYSA-N N-methyl-N-phenyl-2-phenylmethoxy-5-(trifluoromethyl)pyrimidin-4-amine Chemical compound CN(c1ccccc1)c1nc(OCc2ccccc2)ncc1C(F)(F)F SUHGANDNTPOCSQ-UHFFFAOYSA-N 0.000 description 12
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 9
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 description 7
- LLPSANOSMMEMPB-UHFFFAOYSA-N C(C1=CC=CC=C1)OC1=NC=C(C(=N1)Cl)C(F)(F)F Chemical compound C(C1=CC=CC=C1)OC1=NC=C(C(=N1)Cl)C(F)(F)F LLPSANOSMMEMPB-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 7
- 235000019270 ammonium chloride Nutrition 0.000 description 7
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 238000000605 extraction Methods 0.000 description 6
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- BSRNBJFORNUYMG-UHFFFAOYSA-N C(C)(C)(C)OC1=NC=C(C(=N1)N(C)C1=CC=CC=C1)C(F)(F)F Chemical compound C(C)(C)(C)OC1=NC=C(C(=N1)N(C)C1=CC=CC=C1)C(F)(F)F BSRNBJFORNUYMG-UHFFFAOYSA-N 0.000 description 5
- UFVCSVQYWSIFSF-UHFFFAOYSA-N C(C)(C)OC1=NC=C(C(=N1)N(C)C1=CC=CC=C1)C(F)(F)F Chemical compound C(C)(C)OC1=NC=C(C(=N1)N(C)C1=CC=CC=C1)C(F)(F)F UFVCSVQYWSIFSF-UHFFFAOYSA-N 0.000 description 5
- 241001024304 Mino Species 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 3
- CPCHRGFQWZMVNX-UHFFFAOYSA-N 5-(trifluoromethyl)pyrimidine Chemical class FC(F)(F)C1=CN=CN=C1 CPCHRGFQWZMVNX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 0 *c1ncc(C(F)(F)F)c(Cl)n1 Chemical compound *c1ncc(C(F)(F)F)c(Cl)n1 0.000 description 2
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
- ZUCNTELIDFLEJN-UHFFFAOYSA-N C(C1=CC=CC=C1)OC1=NC=C(C(=N1)N(C)C1=CC=C(C=C1)OC(C)(C)C)C(F)(F)F Chemical compound C(C1=CC=CC=C1)OC1=NC=C(C(=N1)N(C)C1=CC=C(C=C1)OC(C)(C)C)C(F)(F)F ZUCNTELIDFLEJN-UHFFFAOYSA-N 0.000 description 2
- MQRGUVIOVNDFBJ-UHFFFAOYSA-N C(CC)OC1=NC=C(C(=N1)N(C)C1=C(C=CC=C1)Br)C(F)(F)F Chemical compound C(CC)OC1=NC=C(C(=N1)N(C)C1=C(C=CC=C1)Br)C(F)(F)F MQRGUVIOVNDFBJ-UHFFFAOYSA-N 0.000 description 2
- NDBATPPGTNSSDQ-UHFFFAOYSA-N C(CC)OC1=NC=C(C(=N1)N(C)C1=C(C=CC=C1)C#N)C(F)(F)F Chemical compound C(CC)OC1=NC=C(C(=N1)N(C)C1=C(C=CC=C1)C#N)C(F)(F)F NDBATPPGTNSSDQ-UHFFFAOYSA-N 0.000 description 2
- IDHDILRZXOPOEN-UHFFFAOYSA-N C(CC)OC1=NC=C(C(=N1)N(C)C1=C(C=CC=C1)Cl)C(F)(F)F Chemical compound C(CC)OC1=NC=C(C(=N1)N(C)C1=C(C=CC=C1)Cl)C(F)(F)F IDHDILRZXOPOEN-UHFFFAOYSA-N 0.000 description 2
- UYTGEHCMKVDZRD-UHFFFAOYSA-N C(CC)OC1=NC=C(C(=N1)N(C)C1=C(C=CC=C1)F)C(F)(F)F Chemical compound C(CC)OC1=NC=C(C(=N1)N(C)C1=C(C=CC=C1)F)C(F)(F)F UYTGEHCMKVDZRD-UHFFFAOYSA-N 0.000 description 2
- SYBXKWPEAXBSKN-UHFFFAOYSA-N C(CC)OC1=NC=C(C(=N1)N(C)C1=C(C=CC=C1)OC(C)(C)C)C(F)(F)F Chemical compound C(CC)OC1=NC=C(C(=N1)N(C)C1=C(C=CC=C1)OC(C)(C)C)C(F)(F)F SYBXKWPEAXBSKN-UHFFFAOYSA-N 0.000 description 2
- KCAVRCSGBFNTSY-UHFFFAOYSA-N C(CC)OC1=NC=C(C(=N1)N(C)C1=C(C=CC=C1)OC(C)C)C(F)(F)F Chemical compound C(CC)OC1=NC=C(C(=N1)N(C)C1=C(C=CC=C1)OC(C)C)C(F)(F)F KCAVRCSGBFNTSY-UHFFFAOYSA-N 0.000 description 2
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
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- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
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- 238000000921 elemental analysis Methods 0.000 description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RMSGQZDGSZOJMU-UHFFFAOYSA-N 1-butyl-2-phenylbenzene Chemical group CCCCC1=CC=CC=C1C1=CC=CC=C1 RMSGQZDGSZOJMU-UHFFFAOYSA-N 0.000 description 1
- BPIUIOXAFBGMNB-UHFFFAOYSA-N 1-hexoxyhexane Chemical compound CCCCCCOCCCCCC BPIUIOXAFBGMNB-UHFFFAOYSA-N 0.000 description 1
- NGQQUXXTDZADNX-UHFFFAOYSA-N 2,3,4,5-tetrachlorofuran Chemical compound ClC=1OC(Cl)=C(Cl)C=1Cl NGQQUXXTDZADNX-UHFFFAOYSA-N 0.000 description 1
- IDRUEHMBFUJKAK-UHFFFAOYSA-N 2,4-dichloro-5-(trifluoromethyl)pyrimidine Chemical compound FC(F)(F)C1=CN=C(Cl)N=C1Cl IDRUEHMBFUJKAK-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
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- MZEHHQYIQLYIAT-UHFFFAOYSA-N COC1=NC=C(C(=N1)N(C)C1=CC=C(C=C1)OCCCCC)C(F)(F)F Chemical compound COC1=NC=C(C(=N1)N(C)C1=CC=C(C=C1)OCCCCC)C(F)(F)F MZEHHQYIQLYIAT-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- OPFTUNCRGUEPRZ-QLFBSQMISA-N Cyclohexane Natural products CC(=C)[C@@H]1CC[C@@](C)(C=C)[C@H](C(C)=C)C1 OPFTUNCRGUEPRZ-QLFBSQMISA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 1
- GNDSIQFCWKHCSI-UHFFFAOYSA-N N-(2-butoxy-3-ethylphenyl)-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine Chemical compound C(CCC)OC1=C(C=CC=C1CC)N(C)C1=NC=NC=C1C(F)(F)F GNDSIQFCWKHCSI-UHFFFAOYSA-N 0.000 description 1
- MEBPZQUGBUNTJF-UHFFFAOYSA-N N-(2-butoxy-3-methylphenyl)-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine Chemical compound C(CCC)OC1=C(C=CC=C1C)N(C)C1=NC=NC=C1C(F)(F)F MEBPZQUGBUNTJF-UHFFFAOYSA-N 0.000 description 1
- WPZUKTYIYBCMEV-UHFFFAOYSA-N N-(3-butoxyphenyl)-2-ethoxy-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine N-(3-butoxyphenyl)-N-methyl-2-propoxy-5-(trifluoromethyl)pyrimidin-4-amine Chemical compound C(CC)OC1=NC=C(C(=N1)N(C)C1=CC(=CC=C1)OCCCC)C(F)(F)F.C(C)OC1=NC=C(C(=N1)N(C)C1=CC(=CC=C1)OCCCC)C(F)(F)F WPZUKTYIYBCMEV-UHFFFAOYSA-N 0.000 description 1
- ZDLJDDOAOPCHEB-UHFFFAOYSA-N N-(3-iodo-2-propoxyphenyl)-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine Chemical compound C(CC)OC1=C(C=CC=C1I)N(C)C1=NC=NC=C1C(F)(F)F ZDLJDDOAOPCHEB-UHFFFAOYSA-N 0.000 description 1
- HZDOIXGDSJLWIQ-UHFFFAOYSA-N N-(4-bromophenyl)-2-cyclopentyloxy-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine N-(4-bromophenyl)-2-hexoxy-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine Chemical compound C(CCCCC)OC1=NC=C(C(=N1)N(C)C1=CC=C(C=C1)Br)C(F)(F)F.C1(CCCC1)OC1=NC=C(C(=N1)N(C)C1=CC=C(C=C1)Br)C(F)(F)F HZDOIXGDSJLWIQ-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- KGTHLJCKWSGDQZ-UHFFFAOYSA-N [Li+].[Na+].CC(C)(C)[O-].CC(C)(C)[O-] Chemical compound [Li+].[Na+].CC(C)(C)[O-].CC(C)(C)[O-] KGTHLJCKWSGDQZ-UHFFFAOYSA-N 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- XTLQJDSCZZMTFE-UHFFFAOYSA-N cyclohexyloxycyclohexane;lithium Chemical compound [Li].C1CCCCC1OC1CCCCC1 XTLQJDSCZZMTFE-UHFFFAOYSA-N 0.000 description 1
- AKOUBXPJKXUSKX-UHFFFAOYSA-N cyclohexyloxycyclohexane;potassium Chemical compound [K].C1CCCCC1OC1CCCCC1 AKOUBXPJKXUSKX-UHFFFAOYSA-N 0.000 description 1
- XZDNOKDWXGNNKZ-UHFFFAOYSA-N cyclohexyloxycyclohexane;sodium Chemical compound [Na].C1CCCCC1OC1CCCCC1 XZDNOKDWXGNNKZ-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012776 electronic material Substances 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229960004592 isopropanol Drugs 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical compound [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-N 0.000 description 1
- WBIUOUBFNXEKBA-UHFFFAOYSA-N lithium;2-methylpropan-1-olate Chemical compound [Li]OCC(C)C WBIUOUBFNXEKBA-UHFFFAOYSA-N 0.000 description 1
- LTRVAZKHJRYLRJ-UHFFFAOYSA-N lithium;butan-1-olate Chemical compound [Li+].CCCC[O-] LTRVAZKHJRYLRJ-UHFFFAOYSA-N 0.000 description 1
- XMAFBJJKWTWLJP-UHFFFAOYSA-N lithium;butan-2-olate Chemical compound [Li+].CCC(C)[O-] XMAFBJJKWTWLJP-UHFFFAOYSA-N 0.000 description 1
- AZVCGYPLLBEUNV-UHFFFAOYSA-N lithium;ethanolate Chemical compound [Li+].CC[O-] AZVCGYPLLBEUNV-UHFFFAOYSA-N 0.000 description 1
- HAUKUGBTJXWQMF-UHFFFAOYSA-N lithium;propan-2-olate Chemical compound [Li+].CC(C)[O-] HAUKUGBTJXWQMF-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000003935 n-pentoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- CBMSDILKECEMOT-UHFFFAOYSA-N potassium;2-methylpropan-1-olate Chemical compound [K+].CC(C)C[O-] CBMSDILKECEMOT-UHFFFAOYSA-N 0.000 description 1
- MKNZKCSKEUHUPM-UHFFFAOYSA-N potassium;butan-1-ol Chemical compound [K+].CCCCO MKNZKCSKEUHUPM-UHFFFAOYSA-N 0.000 description 1
- ZUPDNLCLXSWMAE-UHFFFAOYSA-N potassium;butan-2-olate Chemical compound [K+].CCC(C)[O-] ZUPDNLCLXSWMAE-UHFFFAOYSA-N 0.000 description 1
- AWDMDDKZURRKFG-UHFFFAOYSA-N potassium;propan-1-olate Chemical compound [K+].CCC[O-] AWDMDDKZURRKFG-UHFFFAOYSA-N 0.000 description 1
- WQKGAJDYBZOFSR-UHFFFAOYSA-N potassium;propan-2-olate Chemical compound [K+].CC(C)[O-] WQKGAJDYBZOFSR-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- IKNCGYCHMGNBCP-UHFFFAOYSA-N propan-1-olate Chemical compound CCC[O-] IKNCGYCHMGNBCP-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 125000005920 sec-butoxy group Chemical group 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- JYCDILBEUUCCQD-UHFFFAOYSA-N sodium;2-methylpropan-1-olate Chemical compound [Na+].CC(C)C[O-] JYCDILBEUUCCQD-UHFFFAOYSA-N 0.000 description 1
- SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
- VSCLJRSWEGZJNY-UHFFFAOYSA-N sodium;butan-2-olate Chemical compound [Na+].CCC(C)[O-] VSCLJRSWEGZJNY-UHFFFAOYSA-N 0.000 description 1
- RCOSUMRTSQULBK-UHFFFAOYSA-N sodium;propan-1-olate Chemical compound [Na+].CCC[O-] RCOSUMRTSQULBK-UHFFFAOYSA-N 0.000 description 1
- WBQTXTBONIWRGK-UHFFFAOYSA-N sodium;propan-2-olate Chemical compound [Na+].CC(C)[O-] WBQTXTBONIWRGK-UHFFFAOYSA-N 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
Description
類似の化合物として、2−(4−ニトロフェノキシ)−4−クロロ−5−(トリフルオロメチル)ピリミジン(特許文献1)並びに2−メトキシ−4−クロロ−5−(トリフルオロメチル)ピリミジン(特許文献2)が知られている。
すなわち本発明は、下記一般式(1)
で表される2−アルコキシ−5−(トリフルオロメチル)ピリミジン誘導体に係るものである。
で表わされる2−ベンジルオキシ−5−(トリフルオロメチル)ピリミジン誘導体と、下記一般式(3)
R2O−Metal (3)
(式(3)中、Metalは金属を示し、R2は前記式(1)に同じ)
で表わされる金属アルコキシドとを、反応させる製造方法を提供するものである。
本発明の一般式(1)で表わされる2−アルコキシ−5−(トリフルオロメチル)ピリミジン誘導体でR1が水素原子である化合物としては、具体的には例えば、2−メトキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジン、2−エトキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジン、2−n−プロポキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジン、2−iso−プロポキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジン、2−n−ブトキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジン、2−iso−ブトキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジン、2−sec−ブトキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジン、2−tert−ブトキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジン、2−n−ペントキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジン、2−cyclo−ペントキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジン、2−n−ヘキシルオキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジン、2−cyclo−ヘキシルオキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジン等が挙げられる。
本発明の一般式(2)で表わされる2−ベンジルオキシ−5−(トリフルオロメチル)ピリミジン誘導体でR1が水素原子、メチル基、エチル基又は炭素数3〜6の直鎖若しくは分岐若しくは環式のアルキルである化合物としては、具体的には例えば、2−ベンジルオキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(2−メチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(3−メチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(4−メチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(2−エチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(3−エチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(4−エチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(2−n−プロピルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(3−n−プロピルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(4−n−プロピルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(2−iso−プロピルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(3−iso−プロピルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(4−iso−プロピルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(2−n−ブチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(3−n−ブチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(4−n−ブチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(2−iso−ブチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(3−iso−ブチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(4−iso−ブチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(2−sec−ブチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(3−sec−ブチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(4−sec−ブチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(2−tert−ブチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(3−tert−ブチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(4−tert−ブチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(2−n−ペンチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(3−n−ペンチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(4−n−ペンチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(2−cyclo−ペンチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(3−cyclo−ペンチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(4−cyclo−ペンチルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(2−n−ヘキシルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(3−n−ヘキシルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(4−n−ヘキシルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(2−cyclo−ヘキシルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(3−cyclo−ヘキシルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン、2−ベンジルオキシ−4−[N−メチル−(4−cyclo−ヘキシルフェニル)アミノ]−5−(トリフルオロメチル)ピリミジン等が挙げられる。
本発明の一般式(3)で表わされる金属アルコキド類としては、具体的には例えば、リチウムメトキシド、ナトリウムメトキシド、カリウムメトキシド、リチウムエトキシド、ナトリウムエトキシド、カリウムエトキシド、リチウム−n−プロポキド、ナトリウム−n−プロポキド、カリウム−n−プロポキシド、リチウム−iso−プロポキド、ナトリウム−iso−プロポキド、カリウム−iso−プロポキシド、リチウム−n−ブトキシド、ナトリウム−n−ブトキシド、カリウム−n−ブトキシド、リチウム−iso−ブトキシド、ナトリウム−iso−ブトキシド、カリウム−iso−ブトキシド、リチウム−sec−ブトキシド、ナトリウム−sec−ブトキシド、カリウム−sec−ブトキシド、リチウム−tert−ブトキシド、ナトリウム−tert−ブトキシド、カリウム−tert−ブトキシド、リチウム−n−ペントキシド、ナトリウム−n−ペントキシド、カリウム−n−ペントキシド、リチウム−cyclo−ペントキシド、ナトリウム−cyclo−ペントキシド、カリウム−cyclo−ペントキシド、リチウム−n−ヘキシルオキシド、ナトリウム−n−ヘキシルオキシド、カリウム−n−ヘキシルオキシド、リチウム−cyclo−ヘキシルオキシド、ナトリウム−cyclo−ヘキシルオキシド、カリウム−cyclo−ヘキシルオキシド等が挙げられ、反応に具する一般式(2)で表わされる2−ベンジルオキシ−5−(トリフルオロメチル)ピリミジン誘導体に対して、1.2モル量〜10.0モル量使用するとよい。
なお、分析に当たっては下記機器を使用した。
1H−NMR,19F−NMR,13C−NMR:ブルカー(BRUKER)社製AVANCE II 400。
元素分析:ヤナコ社製CHNコーダー MT−6。
参考例1 2−ベンジルオキシ−4−クロロ−5−(トリフルオロメチル)ピリミジン(4)の調製
1H−NMR(CDCl3,400MHz)δ8.70(d,J=0.8Hz,1H),7.50−7.45(m,2H),7.40−7.32(m,3H),5.50(s,2H)。
19F−NMR(CDCl3,376MHz)δ−63.62。
13C−NMR(CDCl3,100MHz)δ165.94,161.08,158.70(q,J=5.0Hz),135.05,128.75,128.57,122.31(q,J=270.0Hz),117.50(q,J=33.8Hz),70.95。
GC−MS(m/z):288(M+,31),253(35),182(27),107(66),91(100)。
元素分析
計算値 炭素(49.93%)、水素(2.79%)、窒素(9.70%)。
測定値 炭素(19.80%)、水素(2.80%)、窒素(9.68%)。
1H−NMR(CDCl3,400MHz)δ8.40(s,1H),7.46−7.12(m,10H),5.44(s,2H),3.45(s,3H)。
19F−NMR(CDCl3,376MHz)δ−58.23。
13C−NMR(CDCl3,100MHz)δ165.40,162.13,159.31(q,J=6.1Hz),146.22,136.44,129.39,128.47,128.09,127.52,127.19,127.00,123.48(q,J=269.5Hz),105.34(q,J=32.8Hz),69.30,42.71。
GC−MS(m/z)359(M+,18),358(31),268(11),252(13),220(9),106(22),91(100),77(17),65(16)。
1H−NMR(CDCl3,400MHz)δ8.38(s,1H),7.38−7.13(m,5H),4.01(s,3H),3.47(s,3H)。
19F−NMR(CDCl3,376MHz)δ−58.25。
13C−NMR(CDCl3,100MHz)δ165.87,162.17,159.09(q,J=6.1Hz),146.20,129.46,128.54,127.08,123.46(q,J=268.9Hz),105.30(q,J=33.1Hz),55.04,42.75。
GC−MS(m/z)283(35,M+),282(100),267(10),178(13),163(8),106(37),91(7),77(17),51(5)。
実施例1と同じ反応装置を用い、ナトリウムヘキサメチルジシラジド(1.0M−THF溶液、0.912mL,0.912mmol)に替えて、カリウムヘキサメチルジシラジド(1.0M−THF溶液、0.912mL,0.912mmol)を用い、0℃で24時間反応を行った以外は実施例1と同じ操作を行い、粗製物を得た(102.5mg)。得られた粗製物を、ヘキサフルオロベンゼンを内部標準物質として用いた19F−NMRの測定において、目的物の2−メトキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジンの(6)(62.0mg,0.219mmol)が生成していた。(収率72%)。
実施例1と同じ反応装置を用い、ナトリウムヘキサメチルジシラジド(1.0M−THF溶液、0.912mL,0.912mmol)に替えて、リチウムヘキサメチルジシラジド(1.0M−THF溶液、0.912mL,0.912mmol)を用い、70℃で24時間反応を行った以外は実施例1と同じ操作を行い、粗製物を得た(84.8mg)。得られた粗製物を、ヘキサフルオロベンゼンを内部標準物質として用いた19F−NMRの測定において、目的物の2−メトキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジンの(6)(36.2mg,0.128mmol)が生成していた。(収率42%)。
実施例1と同じ反応装置を用い、テトラヒドロフラン(1mL)に替えて、n−ヘキサン(1mL)を用い、20℃で2時間反応を行った以外、実施例1と同じ反応操作を行い、粗製物を得た(105.3mg)。得られた粗製物を、ヘキサフルオロベンゼンを内部標準物質として用いた19F−NMRの測定において、目的物の2−メトキシ−4−(N−メチルフェニルアミノ)−5−(トリフルオロメチル)ピリミジンの(6)(74.1mg,0.262mmol)が生成していた。(収率86%)。
1H−NMR(CDCl3,400MHz)δ8.34(s,1H),7.36−7.12(m,5H),5.26(dq,J=6.2,6.1Hz,1H),3.45(s,3H),1.40(d,J=6.4Hz,6H)。
19F−NMR(CDCl3,376MHz)δ−58.16。
13C−NMR(CDCl3,100MHz)δ165.24,162.30,159.26(q,J=6.2Hz),146.45,129.44,128.58,127.08,123.59(q,J=269.0Hz),105.00(q,J=33.0Hz),71.01,42.68,21.97。
GC−MS(m/z)311(M+,29%),310(33),268(100),252(10),220(10),164(20),150(8),106(57),91(12),77(37)。
1H−NMR(CDCl3,400MHz)δ8.36(s,1H),7.37−7.13(m,5H),3.46(s,3H),1.59(s,9H)。
19F−NMR(CDCl3,376MHz)δ−58.16。
13C−NMR(CDCl3,100MHz)δ165.01,162.11,159.17(q,J=5.9Hz),146.78,129.52,128.60,127.08,123.79(q,J=269.7Hz),104.42(q,J=33.0Hz),81.75,42.87,28.33。
GC−MS(m/z)325(5,M+),310(5),268(100),220(8),177(6),164(18),150(7),106(40),77(24),41(12)。
1H−NMR(CDCl3,400MHz)δ8.37(s,1H),7.28−7.12(m,5H),4.95(m,1H),3.45(s,3H),2.06−1.25(m,10H)。
19F−NMR(CDCl3,376MHz)δ−58.07。
13C−NMR(CDCl3,100MHz)δ165.24,162.27,159.30(q,J=6.1Hz),146.50,129.41,127.10,127.06,123.64(q,J=269.3Hz),104.83(q,J=32.8Hz),76.17,42.54,31.77,25.57,24.10。
GC−MS(m/z)351(11),268(100),253(6),220(5),164(12),106(35),77(18),55(11),41(13)。
Claims (2)
- 下記一般式(1)
で表される2−アルコキシ−5−(トリフルオロメチル)ピリミジン誘導体の製造方法であって、
下記一般式(2)
で表わされる2−ベンジルオキシ−5−(トリフルオロメチル)ピリミジン誘導体と、下記一般式(3)
R2O−Metal (3)
(式(3)中、Metalは金属を示し、R2は前記式(1)に同じ)
で表わされる金属アルコキシドを、反応させる、2−アルコキシ−5−(トリフルオロメチル)ピリミジン誘導体の製造方法。 - 一般式(2)中、R1は、水素原子、メチル基又はエチル基を示す、請求項1に記載の2−アルコキシ−5−(トリフルオロメチル)ピリミジン誘導体の製造方法。
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