Potassium Carbonate → 4-Anilino-5-bromo-2-{4-[2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy]anilino}pyrimidine

HRID 1357529Notes

Reaction equation

HRID 1357529 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH2:7]([CH:9]1[O:11][CH2:10]1)Br.[NH:12]([C:19]1[C:24]([Br:25])=[CH:23][N:22]=[C:21]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=2)[N:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:34][N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1>CS(C)=O>[NH:12]([C:19]1[C:24]([Br:25])=[CH:23][N:22]=[C:21]([NH:26][C:27]2[CH:28]=[CH:29][C:30]([O:33][CH2:10][CH:9]([OH:11])[CH2:7][N:38]3[CH2:39][CH2:40][N:35]([CH3:34])[CH2:36][CH2:37]3)=[CH:31][CH:32]=2)[N:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 18430EpibromohydrinHCID 531671-MethylpiperazineHCID 220481234-Anilino-5-bromo-2-(4-hydroxyanilino)pyrimidine

Product 1

HCID 181865074-Anilino-5-bromo-2-{4-[2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy]anilino}pyrimidineYield 30%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of potassium carbonate (160 mg, 1.1 mmol), epibromohydrin (0.14 ml, 1.7 mmol) and 4-anilino-5-bromo-2-(4-hydroxyanilino)pyrimidine (Method 4, 200 mg, 0.56 mmol) in DMSO (2 ml) was stirred for 12 hours. 1-Methylpiperazine (0.62 ml) was added dropwise and the resulting solution was stirred for a further 12 hours. Silica (1 g) was added and volatile material was removed by evaporation. The residue was loaded onto a Varian Mega Bond Elut column and the column was eluted with 50:50 iso-hexane: DCM (2×20 ml), DCM (2×20 ml), 2% 2M NH3/MeOH/DCM (2×20 ml), 4% 2M NH3/MeOH/DCM (2×20 ml), 6% 2M NH3/MeOH/DCM (2×20 ml) and 10% 2M NH3/MeOH/DCM (8×20 ml). Concentration of the appropriate fractions gave the product as a yellow gum (87 mg, 30%). MS (MH+): 513, 515; HPLC (RT): 1.85.

Workup

  1. stirringthe resulting solution was stirred for a further 12 hours
  2. additionSilica (1 g) was added
  3. customvolatile material was removed by evaporation
  4. washthe column was eluted with 50:50 iso-hexane

Sources & evidence

ORD record
ord-fb06a41a37d1411385cef96da873b70e
Source dataset
uspto-grants-2003_07
Patent number
US06593326B1

Reaction notes

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