Ethanol → Trifluoroacetic acid

HRID 81087Notes

Reaction equation

HRID 81087 reaction equation
[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]

Participants

5

Reactant 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

Product 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

Conditions

Temperature
110 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-077bacc8bcfa4183823fa7d996dbd432
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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