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

HRID 1661607Notes

Reaction equation

HRID 1661607 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-9fd220d0a57d4ca1b4b103b71c3b0b33
Source dataset
uspto-grants-2011_10
Patent number
US08030334B2

Reaction notes

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