Trifluoroacetic acid → 6-[6-methoxy-2-(1-methylcyclopropyl)-1H-indol-3-ylmethyl]pyridine-2-carbonitrile

HRID 2409994Notes

Reaction equation

HRID 2409994 reaction equation
[C:1]([C:3]1[N:8]=[C:7]([CH2:9][CH:10]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=2[NH:25]C(=O)OC(C)(C)C)[C:11]([C:13]2([CH3:16])[CH2:15][CH2:14]2)=O)[CH:6]=[CH:5][CH:4]=1)#[N:2].FC(F)(F)C(O)=O>C(#N)C.ClCCl>[CH3:24][O:23][C:20]1[CH:19]=[C:18]2[C:17]([C:10]([CH2:9][C:7]3[N:8]=[C:3]([C:1]#[N:2])[CH:4]=[CH:5][CH:6]=3)=[C:11]([C:13]3([CH3:16])[CH2:15][CH2:14]3)[NH:25]2)=[CH:22][CH:21]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86703308tert-Butyl {2-[1-(6-cyanopyridin-2-ylmethyl)-2-(1-methylcyclopropyl)-2-oxoethyl]-5-methoxyphenyl}carbamate

Product 1

HCID 867032956-[6-methoxy-2-(1-methylcyclopropyl)-1H-indol-3-ylmethyl]pyridine-2-carbonitrileYield 82.8%

Reagents, catalysts & solvents 1

HCID 21877088Acetonitrile methylene chlorideSolvent

Procedure

To a solution of tert-butyl {2-[1-(6-cyanopyridin-2-ylmethyl)-2-(1-methylcyclopropyl)-2-oxoethyl]-5-methoxyphenyl}carbamate (270 mg) in acetonitrile/dichloromethane (2.1 mL/2.1 mL) was added trifluoroacetic acid (2.1 mL) under ice-cooling, and the mixture was stirred at room temperature for 44.5 hours. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and the resulting mixture was washed with a saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane), and then purified by aminopropylated silica gel column chromatography to obtain the title compound (163 mg). 1H-NMR (CDCl3) δ ppm: 0.70-0.78 (2H, m), 0.81-0.89 (2H, m), 1.33 (3H, s), 3.82 (3H, s), 4.39 (2H, s), 6.70 (1H, dd, J=2.3, 8.5 Hz), 6.80-6.85 (1H, m), 7.12-7.22 (2H, m), 7.47-7.53 (1H, m), 7.59 (1H, t, J=7.8 Hz), 7.87 (1H, br s).

Workup

  1. temperaturecooling
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washthe resulting mixture was washed with a saturated aqueous sodium hydrogen carbonate solution
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)
  8. custompurified by aminopropylated silica gel column chromatography

Sources & evidence

ORD record
ord-668c6dcd15c5433c83b7d61c8a1c46ac
Source dataset
uspto-grants-2014_08
Patent number
US08815903B2

Reaction notes

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