JP2013184893A - トリフルオロメチルピリジノン化合物およびその製造方法 - Google Patents
トリフルオロメチルピリジノン化合物およびその製造方法 Download PDFInfo
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- -1 Trifluoromethyl pyridinone compound Chemical class 0.000 title claims abstract description 50
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 28
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims abstract description 24
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 claims abstract description 14
- 239000011698 potassium fluoride Substances 0.000 claims abstract description 12
- 235000003270 potassium fluoride Nutrition 0.000 claims abstract description 12
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052802 copper Inorganic materials 0.000 claims abstract description 10
- 239000010949 copper Substances 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims abstract description 8
- FHUHWCJWXNYAMP-UHFFFAOYSA-N 1H-pyridin-2-one hydroiodide Chemical class N1C(C=CC=C1)=O.I FHUHWCJWXNYAMP-UHFFFAOYSA-N 0.000 claims description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 238000005481 NMR spectroscopy Methods 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 238000004566 IR spectroscopy Methods 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 150000005299 pyridinones Chemical group 0.000 description 5
- JHDCDEHVUADNKQ-UHFFFAOYSA-N 3-(trifluoromethyl)-1h-pyridin-2-one Chemical compound OC1=NC=CC=C1C(F)(F)F JHDCDEHVUADNKQ-UHFFFAOYSA-N 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- CMGFDWXMBSCUMD-UHFFFAOYSA-N 3,5-diiodo-1-methylpyridin-2-one Chemical compound CN1C=C(I)C=C(I)C1=O CMGFDWXMBSCUMD-UHFFFAOYSA-N 0.000 description 3
- XJANJBWJKFIUTI-UHFFFAOYSA-N 3-iodo-1-methyl-5,6,7,8-tetrahydroquinolin-2-one Chemical compound Cn1c2CCCCc2cc(I)c1=O XJANJBWJKFIUTI-UHFFFAOYSA-N 0.000 description 3
- VKNLXKRZDCJRAG-UHFFFAOYSA-N 3-iodo-1-methyl-6,7-dihydro-5H-cyclopenta[b]pyridin-2-one Chemical compound Cn1c2CCCc2cc(I)c1=O VKNLXKRZDCJRAG-UHFFFAOYSA-N 0.000 description 3
- RMGDJLOUEQWPOU-UHFFFAOYSA-N 3-iodo-1-methylpyridin-2-one Chemical compound CN1C=CC=C(I)C1=O RMGDJLOUEQWPOU-UHFFFAOYSA-N 0.000 description 3
- OOCFODFKYQJDFZ-UHFFFAOYSA-N 5-iodo-1-[(4-methoxyphenyl)methyl]pyridin-2-one Chemical compound COc1ccc(Cn2cc(I)ccc2=O)cc1 OOCFODFKYQJDFZ-UHFFFAOYSA-N 0.000 description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- 239000003905 agrochemical Substances 0.000 description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 3
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000008204 material by function Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- WQULPNIRGWQPQQ-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyridin-2-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C=CC(C(F)(F)F)=C1 WQULPNIRGWQPQQ-UHFFFAOYSA-N 0.000 description 2
- AKSNZYAJXCFOSW-UHFFFAOYSA-N 3-iodo-1-[(4-methoxyphenyl)methyl]-5,6-dihydrobenzo[h]quinolin-2-one Chemical compound COc1ccc(Cn2c-3c(CCc4ccccc-34)cc(I)c2=O)cc1 AKSNZYAJXCFOSW-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 2
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 150000002390 heteroarenes Chemical class 0.000 description 2
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- QHMQWEPBXSHHLH-UHFFFAOYSA-N sulfur tetrafluoride Chemical compound FS(F)(F)F QHMQWEPBXSHHLH-UHFFFAOYSA-N 0.000 description 2
- 238000006692 trifluoromethylation reaction Methods 0.000 description 2
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- KCPDMRDHQWCYAK-UHFFFAOYSA-N 1-methyl-3-(trifluoromethyl)-5,6,7,8-tetrahydroquinolin-2-one Chemical compound Cn1c2CCCCc2cc(c1=O)C(F)(F)F KCPDMRDHQWCYAK-UHFFFAOYSA-N 0.000 description 1
- RXATZPCCMYMPME-UHFFFAOYSA-N 2-chloro-3-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CN=C1Cl RXATZPCCMYMPME-UHFFFAOYSA-N 0.000 description 1
- JFZJMSDDOOAOIV-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C(Cl)N=C1 JFZJMSDDOOAOIV-UHFFFAOYSA-N 0.000 description 1
- YWOWJQMFMXHLQD-UHFFFAOYSA-N 3-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=NC=CC=C1C(F)(F)F YWOWJQMFMXHLQD-UHFFFAOYSA-N 0.000 description 1
- JTZSFNHHVULOGJ-UHFFFAOYSA-N 3-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CN=C1 JTZSFNHHVULOGJ-UHFFFAOYSA-N 0.000 description 1
- BYRJSCNPUHYZQE-UHFFFAOYSA-N 5-(trifluoromethyl)-1h-pyridin-2-one Chemical compound OC1=CC=C(C(F)(F)F)C=N1 BYRJSCNPUHYZQE-UHFFFAOYSA-N 0.000 description 1
- ZDJUNNCVIDKJAN-UHFFFAOYSA-N 5-iodo-1h-pyridin-2-one Chemical compound OC1=CC=C(I)C=N1 ZDJUNNCVIDKJAN-UHFFFAOYSA-N 0.000 description 1
- BLHCMGRVFXRYRN-UHFFFAOYSA-N 6-hydroxynicotinic acid Chemical compound OC(=O)C1=CC=C(O)N=C1 BLHCMGRVFXRYRN-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- AOWRAADERJYXOI-UHFFFAOYSA-N C1=C(C(F)(F)F)C(=O)N(C)C2=C1CCC2 Chemical compound C1=C(C(F)(F)F)C(=O)N(C)C2=C1CCC2 AOWRAADERJYXOI-UHFFFAOYSA-N 0.000 description 1
- ARGRITOUVGQGJQ-UHFFFAOYSA-N C1=CC(OC)=CC=C1CN1C(=O)C(C(F)(F)F)=CC2=C1C1=CC=CC=C1CC2 Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C(C(F)(F)F)=CC2=C1C1=CC=CC=C1CC2 ARGRITOUVGQGJQ-UHFFFAOYSA-N 0.000 description 1
- FRVKYHINCSJCTI-UHFFFAOYSA-N CN1C=C(C(F)(F)F)C=C(C(F)(F)F)C1=O Chemical compound CN1C=C(C(F)(F)F)C=C(C(F)(F)F)C1=O FRVKYHINCSJCTI-UHFFFAOYSA-N 0.000 description 1
- SPTWVURHMGVELS-UHFFFAOYSA-N CN1C=C(I)C=C(C(F)(F)F)C1=O Chemical compound CN1C=C(I)C=C(C(F)(F)F)C1=O SPTWVURHMGVELS-UHFFFAOYSA-N 0.000 description 1
- QWRGLJHUJMVTDM-UHFFFAOYSA-N COC1=CC=C(C=C1)CN2CC=CC(=C2)C(F)(F)F Chemical compound COC1=CC=C(C=C1)CN2CC=CC(=C2)C(F)(F)F QWRGLJHUJMVTDM-UHFFFAOYSA-N 0.000 description 1
- 239000012028 Fenton's reagent Substances 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 102000006239 metabotropic receptors Human genes 0.000 description 1
- 108020004083 metabotropic receptors Proteins 0.000 description 1
- GQJCAQADCPTHKN-UHFFFAOYSA-N methyl 2,2-difluoro-2-fluorosulfonylacetate Chemical compound COC(=O)C(F)(F)S(F)(=O)=O GQJCAQADCPTHKN-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- VGGNVBNNVSIGKG-UHFFFAOYSA-N n,n,2-trimethylaziridine-1-carboxamide Chemical compound CC1CN1C(=O)N(C)C VGGNVBNNVSIGKG-UHFFFAOYSA-N 0.000 description 1
- ZCOGQSHZVSZAHH-UHFFFAOYSA-N n,n-dimethylaziridine-1-carboxamide Chemical compound CN(C)C(=O)N1CC1 ZCOGQSHZVSZAHH-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 1
- 229940071536 silver acetate Drugs 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Abstract
【解決手段】
ヨウ化ピリジノン化合物、ハロゲン化銅、(トリフルオロメチル)トリメチルシランおよびフッ化カリウム、フッ化セシウムおよびtert−ブトキシカリウムからなる群より選ばれる少なくとも1種の塩類を用いて反応させて、トリフルオロメチル基を有する新規ピリジノン化合物を得る。
【選択図】なし
Description
(1)トリフルオロメチル基を有するピリジノン化合物であって、下記式(1)〜(7)で表わされるトリフルオロメチルピリジノン化合物。
5−ヨードピリジン−2−オン(0.44g, 2.0mmol)、炭酸カリウム (0.30g, 2.2mmol)、p−メトキシベンジルクロリド(0.31g, 2.0mmol)をN,N−ジメチルホルムアミド10mL中、25度で一晩撹拌した。反応混合物に水20mLを加えた後、酢酸エチル(20mL×3回)で抽出した。酢酸エチル層を水(20mL×3回)で洗浄した後、無水硫酸マグネシウムで乾燥した。脱水剤をろ過後溶媒留去し、シリカゲルカラムクロマトグラフィー(充填剤 関東化学社製シリカゲル60球状(particle size63−210mm)、展開溶媒 ヘキサン:酢酸エチル=2:1〜1:1(v:v))で精製した。5−ヨード−1−(p−メトキシベンジル)ピリジン−2−オンを黄色油状物として0.56g(収率82%)得た。
フッ化カリウム(0.15g, 2.6mmol)とヨウ化銅(0.50g, 2.6mmol) および5−ヨード−1−(p−メトキシベンジル)ピリジン−2−オン(0.34g, 1.0mmol)をN,N−ジメチルホルムアミド5mlで均一にし、続いて(トリフルオロメチル)トリメチルシラン (0.38 mL, 2.6 mmol)を加えた。反応溶液を80℃で6時間撹拌した。塩化アンモニウム水溶液10mLで希釈した後、酢酸エチル(20mL×3回)で抽出した。酢酸エチル層を無水硫酸マグネシウムで乾燥した後、溶媒を留去し、シリカゲルクロマトグラフィー(充填剤 関東化学社製シリカゲル60球状63−210mm、展開溶媒 ヘキサン:酢酸エチル=4:1〜1:1(v:v))で精製した。式(1)の5−トリフルオロメチル−1−(p−メトキシベンジル)ピリジン−2−オンを白色固体として0.19g得た(収率68%)。
Mp: 48 - 49 ℃ (Mpは融点を表わす。以下同じ)
1H NMR (300 MHz, CDCl3): δ3.81 (s, 3H), 5.01 (s, 2H), 6.65 (d, J=9.6 Hz, 1H), 6.90 (m, 2H), 7.27 (m, 2H), 7.42 (dd, J=9.6, 2.7 Hz, 1H), 7.63 (m, 1H).
13C NMR (75 Hz, CDCl3): δ52.0, 55.1, 109.6 (q, J=34.8 Hz), 114.3, 121.4, 123.2 (q, J=266.6 Hz), 127.1, 129.8, 134.8 (q, J=1.8 Hz), 136.5 (q, J=5.0 Hz), 159.7, 161.8.
19F NMR (282 Hz, CDCl3): δ-63.68 (s).
IR (neat, cm-1): ν3008, 2959, 2840, 1677, 1623, 1514, 1331, 1251, 1167, 1150, 1127.
Anal. Calcd for C14H12F3NO2: C, 59.37; H, 4.27; N, 4.95. Found: C, 58.93; H, 4.36; N, 4.90.
ヨウ化銅(I)を臭化銅(I)に換えた以外は実施例1と同じ条件に付したところ、式(1)の5−トリフルオロメチル−1−(p−メトキシベンジル)ピリジン−2−オンを収率30%で得た。
ヨウ化銅(I)を塩化銅(I)に換えた以外は実施例1と同じ条件に付したところ、式(1)の5−トリフルオロメチル−1−(p−メトキシベンジル)ピリジン−2−オンを収率29%で得た。
フッ化カリウムをtert−ブトキシカリウムに換えた以外は実施例1と同じ条件に付したところ、式(1)の5−トリフルオロメチル−1−(p−メトキシベンジル)ピリジン−2−オンを収率70%で得た。
フッ化カリウムをフッ化セシウムに換えた以外は実施例1と同じ条件に付したところ、式(1)の5−トリフルオロメチル−1−(p−メトキシベンジル)ピリジン−2−オンを収率82%で得た。
基質を3−ヨード−1−メチルピリジン−2−オンを用いた以外は実施例1と同じ条件に付したところ、式(2)の3−(トリフルオロメチル)−1−メチルピリジン−2−オンを白色固体(収率87%)として得た。
Mp: 93 - 94 ℃.
1H NMR (300 MHz, CDCl3): δ3.62 (s, 3H), 6.25 (t, J=7.2 Hz, 1H), 7.55 (d, J=6.9 Hz, 1H), 7.76 (d, J=6.9 Hz, 1H).
13C NMR (75 Hz, CDCl3): δ37.6, 103.8, 119.9 (q, J=31.0 Hz), 122.7 (q, J=271.0 Hz), 138.8 (q, J=5.0 Hz), 142.4, 158.7.
19F NMR (282 Hz, CDCl3): δ67.35 (s).
IR (KBr, cm-1): ν3087, 3053, 3013, 1650, 1569, 1467, 1316, 1126, 1079, 880, 771. Anal. Calcd for C7H6F3NO: C, 47.47; H, 3.41; N, 7.91. Found: C, 47.52; H, 3.18; N, 7.88.
アルゴン置換した反応容器内で、フッ化カリウム(0.15g, 2.6mmol)とヨウ化銅(0.50g, 2.6mmol) および3,5−ジヨード−1−メチルピリジン−2−オン(0.18g, 0.5mmol)をN,N−ジメチルホルムアミド5mlで均一にし、続いて(トリフルオロメチル)トリメチルシラン (0.38 mL, 2.6 mmol)を加えた。反応溶液を室温で48時間撹拌した。塩化アンモニウム水溶液10mLで希釈した後、酢酸エチル(10mL×3回)で抽出した。酢酸エチル層を無水硫酸マグネシウムで乾燥した後、溶媒を留去し、シリカゲルクロマトグラフィー(充填剤 関東化学社製シリカゲル60球状63−210mm、展開溶媒 ヘキサン:酢酸エチル=8:1〜2:1(v:v))で精製した。式(3)の1−メチル−3,5−ビス(トリフルオロメチル)ピリジン−2−オンを白色固体(収率35%)および式(4)の5−ヨード−1−メチル−3−(トリフルオロメチル)ピリジン−2−オンを白色固体(収率57%)としてそれぞれ得た。
Mp: 76 - 77 ℃.
1H NMR (300 MHz, CDCl3): δ3.66 (s, 3H), 7.89 (s, 1H), 7.92 (s, 1H).
13C NMR (75 Hz, CDCl3): δ38.4, 107.9 (q, J=32.0 Hz), 120.7 (q, J=31.0 Hz), 121.9 (q, J=271.0 Hz), 122.6 (q, J=269.8 Hz), 134.9 (m), 141.6 (q, J=5.0 Hz), 158.0.
19F NMR (282 Hz, CDCl3): δ62.84 (s), 67.27 (s).
IR (KBr, cm-1): ν3054, 1636, 1580, 1505, 1417, 1303, 1207, 1117, 892, 752, 686.
Anal. Calcd for C8H5F6NO: C, 39.20; H, 2.06; N, 5.71. Found: C, 38.72; H, 1.99; N, 5.64.
Mp: 135 - 136 ℃.
1H NMR (300 MHz, CDCl3): δ3.59 (s, 3H), 7.77 (s, 1H), 7.84 (s, 1H).
13C NMR (75 Hz, CDCl3): δ37.7, 60.7, 121.6 (q, J=272.3 Hz), 121.7 (q, J=31.0 Hz), 146.1 (q, J=5.0 Hz), 147.2, 157.3.
19F NMR (282 Hz, CDCl3): δ67.41 (s).
IR (KBr, cm-1): ν 3046, 1660, 1593, 1556, 1422, 1303, 1175, 1129, 919, 679.
Anal. Calcd for C7H5F3INO: C, 27.75; H, 1.66; N, 4.62. Found: C, 27.66; H, 1.74; N, 4.48.
基質を3−ヨード−1−メチル−5,6,7,8−テトラハイドロキノリン−2−オンを用いた以外は実施例1と同じ条件に付したところ、式(5)の1−メチル−3−トリフルオロメチル−5,6,7,8−テトラハイドロキノリン−2−オンを白色固体(収率98%)として得た。
Mp: 111 - 112 ℃.
1H NMR (300 MHz, CDCl3): δ1.75 (m, 2H), 1.89 (m, 2H), 2.56 (t, J=6.0 Hz, 2H), 2.68 (t, J=5.7 Hz, 2H), 3.53 (s, 3H), 7.48 (s, 1H).
13C NMR (75 Hz, CDCl3): δ21.2, 21.8, 27.0, 27.6, 30.0, 116.1 (q, J=30.4 Hz), 123.0 (q, J=270.4 Hz), 139.6 (q, J=5.0 Hz), 148.6, 158.7.
19F NMR (282 Hz, CDCl3): δ66.92 (s).
IR (KBr, cm-1): ν 3037, 2948, 2874, 1666, 1606, 1557, 1427, 1323, 1174, 1133, 1100, 1071, 983, 944.
Anal. Calcd for C11H12F3NO: C, 57.14; H, 5.23; N, 6.06. Found: C, 57.20; H, 4.99; N, 6.07.
基質を3−ヨード−1−メチル−1,5,6,7−テトラハイドロシクロペンタ[b]ピリジン−2−オンを用いた以外は実施例1と同じ条件に付したところ、式(6)の1−メチル−3−(トリフルオロメチル)−1,5,6,7−テトラハイドロシクロペンタ[b] ピリジン−2−オンを白色固体として得た(収率99%)。
Mp: 143 - 144 ℃.
1H NMR (300 MHz, CDCl3): δ2.20 (quint., J=7.5 Hz, 2H), 2.83 (t, J=7.5 Hz, 2H), 2.97 (m, 2H), 3.54 (s, 3H), 7.65 (s, 1H).
13C NMR (75 Hz, CDCl3): δ22.2, 29.8, 32.5, 115.8 (q, J=29.2 Hz), 116.9, 123.2 (q, J=271.0 Hz), 135.4 (q, J=5.0 Hz), 155.4, 159.2.
19F NMR (282 Hz, CDCl3): δ66.97 (s).
IR (KBr, cm-1): ν3021, 2918, 2864, 1642, 1577, 1530, 1433, 1231, 791, 753.
Anal. Calcd for C10H10F3NO: C, 55.30; H, 4.64; N, 6.45. Found: C,55.00; H,4.43; N,5.96.
基質を5,6−ジヒドロ−3−ヨード−1−(p−メトキシベンジル)−ベンゾ[h]キノリン−2−オンを用いた以外は実施例1と同じ条件に付したところ、式(7)の5,6−ジヒドロ−1−(p−メトキシベンジル)−3−(トリフルオロメチル)ベンゾ[h]キノリン−2−オンを高粘性黄色油状物として得た(収率98%)。
1H NMR (300 MHz, CDCl3): δ2.92 (m, 4H), 3.80 (s, 3H), 5.57 (s, 2H), 6.90 (d, J=8.7 Hz, 2H), 7.25 (m, 1H), 7.36 (m, 2H), 7.45 (d, J=8.7 Hz, 2H), 7.68 (s, 1H), 8.27 (m, 1H).
13C NMR (75 Hz, CDCl3): δ26.5, 27.9, 55.1, 67.4, 111.1 (q, J=32.2 Hz), 113.7, 123.3 (q, J=271.0 Hz), 123.5, 125.4, 127.0, 127.9, 129.1, 129.2, 129.3, 133.4, 136.3 (q, J=4.4 Hz), 138.5, 152.8, 158.8(q, J=1.9 Hz).
19F NMR (282 Hz, CDCl3): δ64.21 (s).
IR (KBr, cm-1): ν3008, 2940, 2839, 1614, 1515, 1439, 1304, 1274, 1248, 1135, 1078.
Anal. Calcd for C22H18F3NO2: C, 68.57; H, 4.71; N, 3.63. Found: C, 68.39; H, 4.78; N, 3.54.
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