2,4,6-Trimethylaniline → 5-{2-[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-1H-pyrrole-3-carboxylic acid (2,4,6-trimethyl-phenyl)-amide

HRID 1619089Notes

Reaction equation

HRID 1619089 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:11][C:12]1[CH:18]=[C:17]([CH3:19])[CH:16]=[C:15]([CH3:20])[C:13]=1[NH2:14].C([O:23][C:24]([C:26]1[CH:30]=[C:29]([C:31]2[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C:38]3[CH:43]=[CH:42][C:41]([N:44]4[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]4)=[CH:40][C:39]=3[O:51][CH3:52])[N:32]=2)[N:28]([CH3:53])[CH:27]=1)=O)C>C1COCC1>[CH3:11][C:12]1[CH:18]=[C:17]([CH3:19])[CH:16]=[C:15]([CH3:20])[C:13]=1[NH:14][C:24]([C:26]1[CH:30]=[C:29]([C:31]2[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C:38]3[CH:43]=[CH:42][C:41]([N:44]4[CH2:45][CH2:46][N:47]([CH3:50])[CH2:48][CH2:49]4)=[CH:40][C:39]=3[O:51][CH3:52])[N:32]=2)[N:28]([CH3:53])[CH:27]=1)=[O:23]

Participants

5

Reactant 3

HCID 69132,4,6-TrimethylanilineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 666782985-{2-[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-1H-pyrrole-3-carboxylic acid ethyl ester

Product 1

HCID 469179275-{2-[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-1H-pyrrole-3-carboxylic acid (2,4,6-trimethyl-phenyl)-amideYield 73.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

NaHMDS in THF (1.0 M, 11.0 mL, 11.0 mmol) was added over 30 min to a solution of 2,4,6-trimethylaniline (1.2 mL, 8.32 mmol) and 5-{2-[2-methoxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-1H-pyrrole-3-carboxylic acid ethyl ester (1.25 g, 2.77 mmol) in THF (30 mL) at 0° C. The resulting brown solution was stirred at 0° C. for 10 min and allowed to warm to room temperature over a period of 20 min. After stirring at room temperature for 4 h, the reaction was quenched by the addiction of saturated aqueous NH4Cl (10 mL). The reaction was partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer was extracted with ethyl acetate (2×30 mL). The combined organic solution was washed with brine (50 mL), dried over Na2SO4, filtered and evaporated to dryness, the crude solid was purified by flash chromatography on silica gel (eluant: dichloromethane/methanol 95/5) to afford 1.10 g (72% yield) of the title compound.

Workup

  1. temperatureto warm to room temperature over a period of 20 min
  2. stirringAfter stirring at room temperature for 4 h
  3. customthe reaction was quenched by the addiction of saturated aqueous NH4Cl (10 mL)
  4. customThe reaction was partitioned between ethyl acetate (50 mL) and water (50 mL)
  5. extractionThe aqueous layer was extracted with ethyl acetate (2×30 mL)
  6. washThe combined organic solution was washed with brine (50 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customthe crude solid was purified by flash chromatography on silica gel (eluant: dichloromethane/methanol 95/5)

Sources & evidence

ORD record
ord-82dc3e42c951433a8d74d95398986add
Source dataset
uspto-grants-2014_07
Patent number
US08772280B2

Reaction notes

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