Water → HCID 50906786, compound

HRID 1431331Notes

Reaction equation

HRID 1431331 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:12]([NH:13][C:14]3[C:23]4[C:18](=[CH:19][C:20]([F:25])=[CH:21][C:22]=4[F:24])[N:17]=[C:16]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=4)[C:15]=3[CH3:32])=[CH:11][C:10]([N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[CH:9][N:8]=2)[CH2:3][CH2:2]1.I[CH2:40][CH3:41].[H-].[Na+].O>CN(C)C=O>[N:4]1([C:7]2[C:12]([N:13]([CH2:40][CH3:41])[C:14]3[C:23]4[C:18](=[CH:19][C:20]([F:25])=[CH:21][C:22]=4[F:24])[N:17]=[C:16]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=4)[C:15]=3[CH3:32])=[CH:11][C:10]([N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[CH:9][N:8]=2)[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 6340IodoethaneHCID 24758Sodium hydrideHCID 59631375HCID 59631375, compound

Product 1

HCID 50906786HCID 50906786, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of N-(2,5-dimorpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine (0.050 g, 0.096 mmol), in N,N-dimethylformamide (1.0 mL) was added iodoethane (0.030 g, 0.193 mmol) followed by 60% sodium hydride (7.71 mg, 0.193 mmol). The reaction was heated to 60° C. and stirring continued for 41 h. Water was added to quench the reaction and the resulting mixture was extracted with EtOAc (3×10 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography on basic alumina (0-50% EtOAc/hexane) to give N-(2,5-di-4-morpholinyl-3-pyridinyl)-N-ethyl-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, CDCl3) δ ppm 8.66 (1H, d, J=4.3 Hz), 8.02 (1H, s), 7.83-7.90 (1H, m), 7.77-7.83 (1H, m), 7.61-7.69 (2H, m), 7.35 (1H, ddd, J=7.4, 4.9, 1.4 Hz), 6.86-7.00 (2H, m), 3.77-3.98 (6H, m), 3.21 (4H, br. s.), 2.95 (4H, s), 2.88 (3H, s), 2.48 (4H, br. s.), 2.12 (3H, s). Mass Spectrum (ESI) m/e=547.3 (M+1).

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe resulting mixture was extracted with EtOAc (3×10 mL)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography on basic alumina (0-50% EtOAc/hexane)

Sources & evidence

ORD record
ord-fd5e93f62c084750b65f1750d2158f16
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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