反应详情

N4-[5-Chloro-4-(1-methylindol-3-yl)pyrimidin-2-yl]-N1-(2-dimethylaminoethyl)-5-methoxy-N1-methylbenzene-1,2,4-triamine (Intermediate 97, 250 mg, 0.52 mmol), zinc (3.41 mg, 0.05 mmol), tris(dibenzylideneacetone)dipalladium(0) (47.7 mg, 0.05 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (‘XPhos’, 49.7 mg, 0.10 mmol), and dicyanozinc (36.7 mg, 0.31 mmol) were placed in a reaction tube under N2 and then degassed DMA (1.38 mL) was added. The resulting suspension was shined for 3.5 h at 95° C. The mixture was then diluted with EtOAc and washed 5 times with water, and then brine. The solution was then dried (MgSO4) and concentrated in vacuo. The residue was dissolved in CH3OH/CH2Cl2 and the solution was allowed to pass through a stratospheres SPE cartridge PL-Thiol MP SPE (available from Polymer Laboratories)under gravity. The resulting solution was concentrated in vacuo and the residue was triturated with diethyl ether. The resulting solid was collected by filtration and washed with diethyl ether to give the title compound (80 mg) as yellow solid. The aqueous work-up solutions were purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M methanolic ammonia and pure fractions were concentrated in vacuo to give a brown oil (126 mg). Purification by FCC, eluting with 0-5% methanolic ammonia in CH2Cl2 gave the title compound (94 mg) as a yellow solid. Both batches of product were combined to give (174 mg, 71%) as a yellow solid; m/z: ES+ MH+ 471.33.

1. washwashed 5 times with water
2. dry with materialThe solution was then dried (MgSO4)
3. concentrationconcentrated in vacuo
4. dissolutionThe residue was dissolved in CH3OH/CH2Cl2
5. concentrationThe resulting solution was concentrated in vacuo
6. customthe residue was triturated with diethyl ether
7. filtrationThe resulting solid was collected by filtration
8. washwashed with diethyl ether