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

HRID 1357530Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].[NH:7]([C:14]1[C:19]([Br:20])=[CH:18][N:17]=[C:16]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=2)[N:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.Cl.Cl.[CH3:31][N:32]1[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][CH2:40]Cl)[CH2:34][CH2:33]1>CS(C)=O>[NH:7]([C:14]1[C:19]([Br:20])=[CH:18][N:17]=[C:16]([NH:21][C:22]2[CH:23]=[CH:24][C:25]([O:28][CH2:40][CH2:39][CH2:38][N:35]3[CH2:36][CH2:37][N:32]([CH3:31])[CH2:33][CH2:34]3)=[CH:26][CH:27]=2)[N:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of potassium carbonate (180 mg, 1.3 mmol), 4-anilino-5-bromo-2-(4-hydroxyanilino)pyrimidine (Method 4, 150 mg, 0.42 mmol) and 3-(4-methyl-1-piperazinyl)propyl chloride dihydrochloride (120 mg, 0.48 mmol) in DMSO (2 ml) was heated at 100° C. for 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 solid (35 mg, 17%). MS (MH+): 497, 499; HPLC (RT): 2.74.

Workup

additionSilica (1 g) was added
customvolatile material was removed by evaporation
washthe column was eluted with 50:50 iso-hexane

Sources & evidence

ORD record: ord-2a180279670a4a2aaad9f6bea9c29f5d
Source dataset: uspto-grants-2003_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06593326B1

Reaction notes

Loading…