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

HRID 2409992Notes

Reaction equation

HRID 2409992 reaction equation
[C:1]([C:3]1[N:8]=[C:7]([CH2:9][CH:10]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:17]=2[NH:24]C(=O)OC(C)(C)C)[C:11](=O)[CH:12]([CH3:14])[CH3:13])[CH:6]=[CH:5][CH:4]=1)#[N:2].FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+]>ClCCl>[CH:12]([C:11]1[NH:24][C:17]2[C:16]([C:10]=1[CH2:9][C:7]1[N:8]=[C:3]([C:1]#[N:2])[CH:4]=[CH:5][CH:6]=1)=[CH:21][CH:20]=[C:19]([O:22][CH3:23])[CH:18]=2)([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 86703307tert-Butyl {2-[1-(6-cyanopyridin-2-ylmethyl)-3-methyl-2-oxobutyl]-5-methoxyphenyl}carbamate

Product 1

HCID 867033096-(2-Isopropyl-6-methoxy-1H-indol-3-ylmethyl)pyridine-2-carbonitrileYield 93.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl {2-[1-(6-cyanopyridin-2-ylmethyl)-3-methyl-2-oxobutyl]-5-methoxyphenyl}carbamate (269 mg) in dichloromethane (13 mL) was added trifluoroacetic acid (2.6 mL) under ice-cooling, and the mixture was stirred at room temperature for 2.75 hours. To the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution. The organic layer was separated, washed with saturated brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (181 mg). 1H-NMR (CDCl3) δ ppm: 1.28 (6H, d, J=7.0 Hz), 3.21-3.35 (1H, m), 3.83 (3H, s), 4.26 (2H, s), 6.73 (1H, dd, J=2.3, 8.8 Hz), 6.86 (1H, d, J=2.3 Hz), 7.19-7.29 (2H, m), 7.45-7.52 (1H, m), 7.55-7.64 (1H, m), 7.80 (1H, br s).

Workup

  1. temperaturecooling
  2. customThe organic layer was separated
  3. washwashed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-1642c346eddb44a3bba73950a2ec78d9
Source dataset
uspto-grants-2014_08
Patent number
US08815903B2

Reaction notes

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