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

HRID 1619085Notes

Reaction equation

HRID 1619085 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)[CH:6]=[CH:5][C:4]=1[NH:16][C:17]1[N:22]=[C:21]([C:23]2[N:27]([CH2:28]C)[CH:26]=[C:25]([C:30]([OH:32])=O)[CH:24]=2)[CH:20]=[CH:19][N:18]=1.C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:64]([C:66]1[CH:72]=[CH:71][CH:70]=[C:69]([CH2:73][CH3:74])[C:67]=1[NH2:68])[CH3:65]>CN(C)C=O.C(OCC)(=O)C>[CH2:64]([C:66]1[CH:72]=[CH:71][CH:70]=[C:69]([CH2:73][CH3:74])[C:67]=1[NH:68][C:30]([C:25]1[CH:24]=[C:23]([C:21]2[CH:20]=[CH:19][N:18]=[C:17]([NH:16][C:4]3[CH:5]=[CH:6][C:7]([N:9]4[CH2:10][CH2:11][N:12]([CH3:15])[CH2:13][CH2:14]4)=[CH:8][C:3]=3[O:2][CH3:1])[N:22]=2)[N:27]([CH3:28])[CH:26]=1)=[O:32])[CH3:65]

Participants

7

Reactant 4

HCID 113692,6-DiethylanilineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 666874105-{2-[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-ethyl-1H-pyrrole-3-carboxylic acid

Product 1

HCID 469172745-{2-[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-1H-pyrrole-3-carboxylic acid (2,6-diethyl-phenyl)-amideYield 23.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 5-{2-[2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-ethyl-1H-pyrrole-3-carboxylic acid (75 mg, 0.178 mmol) in anhydrous dimethylformamide (5 mL) was treated with N-ethyl-N,N-diisopropylamine (0.3 mL, 1.775 mmol) and TBTU (91 mg, 0.284 mmol). The mixture was then treated with 2,6-diethylaniline (0.3 mL, 1.775 mmol). The resulting mixture was stirred at 80° C. for 4 hours under argon. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (20 mL), washed with a saturated aqueous solution of sodium hydrogen carbonate (20 mL), brine, dried over anhydrous Na2SO4 and concentrated. Purification by flash chromatography on silica gel (eluant: dichloromethane/methanol 95/5) afforded 23 mg (23%) of the title compound.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with a saturated aqueous solution of sodium hydrogen carbonate (20 mL), brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customPurification by flash chromatography on silica gel (eluant: dichloromethane/methanol 95/5)

Sources & evidence

ORD record
ord-86b3c2fcc69642278ce42c4b6ed980ee
Source dataset
uspto-grants-2014_07
Patent number
US08772280B2

Reaction notes

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