Iodoethane → 1-ethyl-2-pyridin-3-yl-1H-indole-3-carbonitrile

HRID 593562Notes

Reaction equation

HRID 593562 reaction equation
[C:1]([CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][C:11](=O)[C:12]1[CH:17]=[CH:16][CH:15]=[N:14][CH:13]=1)#[N:2].C([O-])([O-])=O.[Cs+].[Cs+].I[CH2:26][CH3:27]>CN(C=O)C>[CH2:26]([N:10]1[C:5]2[C:4](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:3]([C:1]#[N:2])=[C:11]1[C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)[CH3:27]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 10796Cesium carbonateHCID 59534663N-(2-cyanomethyl-phenyl)-nicotinamide

Product 1

HCID 582157761-ethyl-2-pyridin-3-yl-1H-indole-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of N-(2-cyanomethyl-phenyl)-nicotinamide (Example 83a, 400 mg, 1.69 mmol) in DMF (17 mL) is added Cs2CO3 (1.1 g, 3.37 mmol). The reaction is heated to 80° C., at which time a solution of iodoethane (0.14 mL, 1.75 mmol) in DMF (5 mL) is added over 75 min. The temperature is then increased to 100° C. After stirring for an additional 2 h, the reaction is cooled to room temperature and quenched with saturated aqueous NH4Cl, and diluted with ethyl acetate and water. The layers are separated and the aqueous layer is extracted with ethyl acetate. The combined organic extracts are dried over sodium sulfate, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 3:10 to 1:0) to furnish 1-ethyl-2-pyridin-3-yl-1H-indole-3-carbonitrile. 1H NMR (400 MHz, CDCl3) δ ppm 1.40 (t, J=7.2 Hz, 3H), 4.22 (q, J=7.2 Hz, 2H), 7.32-7.45 (m, 2H), 7.47-7.51 (m, 1H), 7.54 (dd, J=7.8, 5.6 Hz, 1H), 7.82 (d, J=7.8 Hz, 1H), 7.91-7.98 (m, 1H), 8.78-8.85 (m, 2H). HRMS (ESI) m/z 248.1190 [(M+H)+ Calcd for C16H14N3: 248.1188].

Workup

  1. additionis added over 75 min
  2. temperaturethe reaction is cooled to room temperature
  3. customquenched with saturated aqueous NH4Cl
  4. additiondiluted with ethyl acetate and water
  5. customThe layers are separated
  6. extractionthe aqueous layer is extracted with ethyl acetate
  7. dry with materialThe combined organic extracts are dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 3:10 to 1:0)

Sources & evidence

ORD record
ord-a481a7908c7f4657b643cab9c863535b
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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