2-Amino-4-chloro-6-methylpyrimidine → HCID 58504494, compound

Participants

Reaction Conditions

Reaction Steps

To (3,5-difluoro-4-formylphenyl)boronic acid (5.0 g, 26.9 mmol) and 4-chloro-6-methyl-2-pyrimidinamine (3.86 g, 26.9 mmol) were added 1,4-dioxane (100 mL) and saturated aqueous NaHCO3 (40 mL). The mixture was degassed with nitrogen for 10 minutes. Pd(Ph3P)4 (1.0 g, 0.87 mmol) was added and the reaction mixture was stirred overnight at 100° C. The reaction mixture was cooled to room temperature, poured onto water and filtered. The solid was washed with water and EtOAc to provide a pale yellow solid (2.4 g). The combined filtrates were poured into a separatory funnel. The organic layer was separated and the aqueous layer was further extracted with EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated. The resulting residue was chromatographed on a SiO2 column (gradient: 100% CHCl3 to 90:10:1 CHCl3/CH3OH/NH4OH). Loading of the material into the column was complicated by the poor solubility properties of the residue. Hot dioxane was used to help solubilize the residue. Part of the material co-eluted with the solvent front. All the fractions containing the product (including the ones that co-eluted with the solvent front) were combined, concentrated and triturated with ˜1:1 mixture of EtOAc and hexanes to provide desired product as a yellow solid (1.6 g). This material was combined with the pale yellow solid obtained from the initial filtration and used without further purification. LC-MS (ES) m/z=250 [M+H]+.

Provenance & Evidence