Imatinib amine → 4-(dichloromethyl)-N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)benzamide

Temperature

45 °C

To a suspension of 4-methyl-N*3*-(4-pyridin-3-yl-pyrimidin-2-yl)-benzene-1,3-diamine (2.00 g mg, 7.21 mmol) in toluene (22 ml) at 45° C. under an atmosphere of argon is added sequentially 4-dichloromethyl-benzoic acid methyl ester (1.90 g, 8.67 mmol) and AlMe3 (2 M in toluene, 12.6 ml, 25.2 mmol). The resulting brown solution is stirred at 45° C. for a period of 3.5 hrs. The reaction mixture is then cooled to 0° C. and quenched by slow addition of a saturated aqueous solution of Rochelle salt (70 ml) which causes the precipitation of the crude product. t-Butyl methyl ether (150 ml) and methylene chloride (100 ml) are added sequentially to the suspension which are then washed with aqueous saturated NaHCO3 (100 ml) and aqueous saturated NaCl (100 ml). The aqueous phases are back-extracted with t-butyl methyl ether (100 ml). The crude product, which is contained in the combined organic phases, is filtered off with suction, washed with t-butyl methyl ether and dried in vacuo. Yield: 3.35 g of the title compound, 84% of theory, as beige crystals, (HPLC: 91% area).

1. temperatureThe reaction mixture is then cooled to 0° C.
2. customquenched by slow addition of a saturated aqueous solution of Rochelle salt (70 ml) which
3. customthe precipitation of the crude product
4. additiont-Butyl methyl ether (150 ml) and methylene chloride (100 ml) are added sequentially to the suspension which
5. washare then washed with aqueous saturated NaHCO3 (100 ml) and aqueous saturated NaCl (100 ml)
6. extractionThe aqueous phases are back-extracted with t-butyl methyl ether (100 ml)
7. filtrationis filtered off with suction
8. washwashed with t-butyl methyl ether
9. customdried in vacuo

ORD record

ord-b024b39ea23049e9b4d3ab68d50fcca1

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07816359B2