Ethanol → Trifluoroacetic acid

HRID 1852694ノート

反応式

HRID 1852694 の反応式
[CH:1]1([C@H:5]([NH:7][C:8]2[C:13]3[N:14]([CH2:26][C:27]4[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=4)[C:15]([C:17]4[CH:22]=[C:21]([CH:23]([CH3:25])[CH3:24])[CH:20]=[CH:19][N:18]=4)=[N:16][C:12]=3[C:11](C)=[C:10](C#N)[N:9]=2)[CH3:6])[CH2:4][CH2:3][CH2:2]1.[OH-:40].[Na+].[CH2:42]([OH:44])[CH3:43]>>[CH:1]1([C@H:5]([NH:7][C:8]2[C:13]3[N:14]([CH2:26][C:27]4[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=4)[C:15]([C:17]4[CH:22]=[C:21]([CH:23]([CH3:25])[CH3:24])[CH:20]=[CH:19][N:18]=4)=[N:16][C:12]=3[C:11]([CH3:10])=[C:43]([C:42]([OH:40])=[O:44])[N:9]=2)[CH3:6])[CH2:4][CH2:3][CH2:2]1.[C:30]([OH:44])([C:33]([F:36])([F:35])[F:34])=[O:40]

参加物

5

反応物 3

HCID 702EthanolHCID 14798Sodium HydroxideHCID 86724465(R)-4-((1-cyclobutylethyl)amino)-2-(4-isopropylpyridin-2-yl)-7-methyl-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile

生成物 2

HCID 6422Trifluoroacetic acidHCID 86724466(R)-4-((1-cyclobutylethyl)amino)-2-(4-isopropylpyridin-2-yl)-7-methyl-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carboxylic acid

反応条件

温度
110 °C

実験手順

To (R)-4-((1-cyclobutylethyl)amino)-2-(4-isopropylpyridin-2-yl)-7-methyl-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (26 mg, 0.049 mmol) dissolved in ethanol (1 ml) was added sodium hydroxide (5.0 M in water, 1 mL, 5.0 mmol). The reaction was heated to 110° C. and stirred overnight. The solution was cooled to room temperature, concentrated, and then diluted with EtOAc. It was washed with 1N HCl, then dried over sodium sulfate, filtered and concentrated. The residue was purified by mass triggered, reverse phase (C-18) preparative HPLC (acetonitrile:water: 0.1% v/v trifluoroacetic acid modifier) to afford (R)-4-((1-cyclobutylethyl)amino)-2-(4-isopropyl pyridin-2-yl)-7-methyl-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carboxylic acid (as a TFA salt). MS ESI calc'd for C30H32F3N5O2 [M+H]+ 552. found 552. 1H NMR (500 MHz, CDCl3): δ 0.99 (d, J=6.1 Hz, 3H); 1.32-1.25 (m, 1H); 1.35 (d, J=6.9 Hz, 6H); 1.50-1.42 (m, 1H); 1.63-1.54 (m, 2H); 1.78-1.67 (m, 1H); 1.92-1.85 (m, 1H); 2.06-1.99 (m, 1H); 2.89 (s, 3H); 3.08-3.02 (m, 1H); 3.81 (s, 1H); 5.30 (s, 1H); 6.36 (d, J=17.1 Hz, 1H); 6.59 (d, J=16.8 Hz, 1H); 7.29-7.27 (m, 1H); 7.33 (d, J=8.0 Hz, 2H); 7.68 (d, J=8.0 Hz, 2H); 8.33 (s, 1H); 8.45 (d, J=5.0 Hz, 1H).

後処理

  1. temperatureThe solution was cooled to room temperature
  2. concentrationconcentrated
  3. additiondiluted with EtOAc
  4. washIt was washed with 1N HCl
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by mass

出典と根拠

ORDレコード
ord-416204d3c58646b186ca5a6884df1e9e
出典データセット
uspto-grants-2015_02
特許番号
US08962611B2

反応ノート

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