Iodoethane → N-ethyl-5,7-difluoro-3-methyl-N-(5-(4-morpholinyl)-3-pyridinyl)-2-(2-pyridinyl)-4-quinolinamine

HRID 1431398Notes

Reaction equation

HRID 1431398 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([NH:20][C:21]1[CH:22]=[N:23][CH:24]=[C:25]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[CH:26]=1)=[C:5]([CH3:19])[C:6]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1)=[N:7]2.[H-].[Na+].I[CH2:36][CH3:37]>CN(C)C=O>[CH2:36]([N:20]([C:21]1[CH:22]=[N:23][CH:24]=[C:25]([N:27]2[CH2:28][CH2:29][O:30][CH2:31][CH2:32]2)[CH:26]=1)[C:4]1[C:3]2[C:8](=[CH:9][C:10]([F:12])=[CH:11][C:2]=2[F:1])[N:7]=[C:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[C:5]=1[CH3:19])[CH3:37]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 509067895,7-difluoro-3-methyl-N-(5-morpholinopyridin-3-yl)-2-(pyridin-2-yl)quinolin-4-amine

Product 1

HCID 59631304N-ethyl-5,7-difluoro-3-methyl-N-(5-(4-morpholinyl)-3-pyridinyl)-2-(2-pyridinyl)-4-quinolinamine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 5,7-difluoro-3-methyl-N-(5-morpholinopyridin-3-yl)-2-(pyridin-2-yl)quinolin-4-amine (0.06 g, 0.14 mmol) in N,N-dimethylformamide (1.4 mL) was added sodium hydride (0.011 g, 0.28 mmol) followed by iodoethane (0.043 g, 0.28 mmol). Stirring continued at 60° C. for 2 h. After which the reaction was quenched with water (25 mL). The mixture was extracted with EtOAc (2×10 mL) and DCM (1×10 mL). The organic layers were combined and washed with brine (1×20 mL) and dried over magnesium sulfate. The crude product was purified by column chromatography on basic alumina (0 to 50% EtOAc in hexane) to give the desired product N-ethyl-5,7-difluoro-3-methyl-N-(5-(4-morpholinyl)-3-pyridinyl)-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.74 (1H, d, J=4.7 Hz), 7.83-7.96 (2H, m), 7.74 (2H, m), 7.34-7.50 (2H, m), 7.26 (1H, br. s), 6.93-7.04 (1H, m), 6.31 (1H, br s), 3.77-3.94 (5H, m), 3.70 (1H, m), 3.10 (4H, br. s), 2.33-2.40 (3H, s), 1.29 (3H, t, J=7.2 Hz). Mass Spectrum (ESI) m/e=462.2 (M+1).

Workup

  1. customAfter which the reaction was quenched with water (25 mL)
  2. extractionThe mixture was extracted with EtOAc (2×10 mL) and DCM (1×10 mL)
  3. washwashed with brine (1×20 mL)
  4. dry with materialdried over magnesium sulfate
  5. customThe crude product was purified by column chromatography on basic alumina (0 to 50% EtOAc in hexane)

Sources & evidence

ORD record
ord-2d6db0d629404080935bc104b1bb5701
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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