(Trifluoromethyl)trimethylsilane → N-(5-(5-(3-hydroxy-3-(trifluoromethyl)cyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 1497915

反応式

HRID 1497915 の反応式
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([CH:13]3[CH2:16][C:15](=[O:17])[CH2:14]3)[O:10][N:9]=2)=[CH:4][C:3]=1[NH:18][C:19]([C:21]1[N:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]2=[N:23][CH:22]=1)=[O:20].[F:30][C:31]([Si](C)(C)C)([F:33])[F:32].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[OH:17][C:15]1([C:31]([F:33])([F:32])[F:30])[CH2:16][CH:13]([C:11]2[O:10][N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([NH:18][C:19]([C:21]4[N:25]5[CH:26]=[CH:27][CH:28]=[CH:29][C:24]5=[N:23][CH:22]=4)=[O:20])[CH:4]=3)[N:12]=2)[CH2:14]1

参加物

5

反応物 3

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium Fluoride2 回HCID 71280448N-(2-methyl-5-(5-(3-oxocyclobutyl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

生成物 1

HCID 71280426N-(5-(5-(3-hydroxy-3-(trifluoromethyl)cyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a stirring solution of N-(2-methyl-5-(5-(3-oxocyclobutyl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide (10) (150 mg, 0.387 mmol) in ahydrous THF (2.5 mL) at 0° C. was added trifluoromethyltrimethylsilane (121 μL, 0.774 mmol) and TBAF (100 μL in THF and 5% water). The reaction was stirred to room temperature for 3 hours. Then TBAF (0.5 mL in THF and 5% water) was added and the reaction was stirred for 1 hour. The solvent was concentrated and the crude product was dissolved in ethyl acetate. The organic phase was washed with a water, brine and dried over anhydrous sodium sulfate. The crude product was purified by silica chromatography to yield N-(5-(5-(3-hydroxy-3-(trifluoromethyl)cyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (F25). 1H NMR (400 MHz, d6-DMSO) δ 10.04 (s, 1H), 9.47-9.45 (m, 1H), 8.60 (s, 1H), 8.09 (d, J=1.6 Hz, 1H), 7.83 (dd, J=2.0, 8.0 Hz, 1H), 7.80-7.78 (m, 1H), 7.55-7.50 (m, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.20-7.16 (m, 1H), 6.92 (s, 1H), 3.32-3.28 (m, 1H), 2.99-2.93 (m, 2H), 2.68-2.60 (m, 2H), 2.37 (s, 3H). MS m/z 458.41 (M+1)+.

後処理

  1. stirringthe reaction was stirred for 1 hour
  2. concentrationThe solvent was concentrated
  3. dissolutionthe crude product was dissolved in ethyl acetate
  4. washThe organic phase was washed with a water, brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe crude product was purified by silica chromatography

出典と根拠

ORDレコード
ord-c4a29c78ace945b293ec0152b28d17c4
出典データセット
uspto-grants-2015_12
特許番号
US09199981B2

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