Methyl iodide → 5-{2-[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-1H-pyrrole-3-carboxylic acid ethyl ester

HRID 1619087Notes

Reaction equation

HRID 1619087 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)=[CH:20][C:19]=3[O:31][CH3:32])[N:12]=2)[NH:8][CH:7]=1)=[O:5])[CH3:2].[H-].[Na+].[CH3:35]I>O1CCCC1.CS(C)=O>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([N:24]4[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]4)=[CH:20][C:19]=3[O:31][CH3:32])[N:12]=2)[N:8]([CH3:35])[CH:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 666783025-{2-[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1H-pyrrole-3-carboxylic acid ethyl ester

Product 1

HCID 666782985-{2-[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-1H-pyrrole-3-carboxylic acid ethyl esterYield 74.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-{2-[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1H-pyrrole-3-carboxylic acid ethyl ester (0.5 g, 1.14 mmol) in tetrahydrofuran (25 mL) and dimethylsulfoxide (5 mL) cooled in a ice-water bath, NaH (50 mg, 1.26 mmol) and methyl iodide (0.08 mL, 1.26 mmol) were added. The reaction was continued at room temperature for 12 h, tetrahydrofuran was removed under vacuo, then dichloromethane (25 mL) was added and the organic phase washed with water (25 mL). The aqueous fraction was extracted with dichloromethane (2×20 mL). The organic fractions were combined, dried over sodium sulfate, filtered, and concentered in vacuo. Purification by flash chromatography on silica gel (eluant: dichloromethane/methanol 95/5) provided 382 mg (74%) of the title compound as a pale yellow solid.

Workup

  1. customtetrahydrofuran was removed under vacuo
  2. additiondichloromethane (25 mL) was added
  3. washthe organic phase washed with water (25 mL)
  4. extractionThe aqueous fraction was extracted with dichloromethane (2×20 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customPurification by flash chromatography on silica gel (eluant: dichloromethane/methanol 95/5)

Sources & evidence

ORD record
ord-21d7ab93cc9244c6a097d751cefb7f1e
Source dataset
uspto-grants-2014_07
Patent number
US08772280B2

Reaction notes

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