Sodium Carbonate → HCID 22317669, compound

Participants

Reaction Conditions

Reaction Steps

The title compound was prepared from rac-3-{6-methyl-2-[2-(tetrahydro-pyran-2-yloxy)-ethylamino]-pyrimidin-4-yl}-benzoic acid methyl ester [prepared by the following procedure: A mixture of 3-carboxyphenylboronic acid (8.3 g, 50.0 mmol), 2,4-dichloro-6-methylpyrimidine (8.15 g, 50.0 mmol) and Na2CO3 (9.5 g, 90 mmol) in acetonitrile (160 ml)/H2O (80 ml) was degassed and Pd(PPh3)4 (0.87 g, 0.75 mmol) was added. The mixture was stirred for 18 h at 85° C. in an atmosphere of nitrogen and then concentrated in vacuum to a volume of ca.100 ml H2O (100 ml) was added and the mixture was washed with AcOEt (50 ml). The pH of the aqueous phase was set to 2.5 by addition of 25% HCl and the precipitate was collected and dried to give 3-(2-chloro-6-methyl-pyrimidin-4-yl)-benzoic acid (9.1 g) as a white solid. A sample of this material (1.49 g, 6 mmol) was heated in 2-amino-ethanol (3.6 ml) at 80° C. for 1 h. The mixture was evaporated in vacuum and the residual oil was stirred in 1N HCl-MeOH (20 ml) for 18 h at 40° C. The crude product (1.36 g) and 3,4-dihydro-2H-pyran (0.86 ml, 9.5 mmol) were stirred in AcOEt (10 mL)/4N HCl-Et2O (1.3 ml) for 4 h at RT The mixture was diluted with AcOEt and washed with sat. NaHCO3-sol. and brine. The organic layer was dried over Na2SO4, evaporated in vacuum, and the residue was purified by chromatography (silica gel, AcOEt/hexane 1:1) to give the methyl ester as light yellow oil (1.53 g).] (1.53 g, 4.1 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a light yellow oil (1.62 g).

Provenance & Evidence