Ethanol → Trifluoroacetic acid

HRID 81087노트

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HRID 81087 반응식
[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]

참가 물질

5

반응물 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

생성물 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

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온도
110 °C

실험 절차

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-isopropylpyridin-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).

후처리

  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

출처 및 근거

ORD 기록
ord-077bacc8bcfa4183823fa7d996dbd432
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846657B2

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