Hydrochloric Acid → HCID 22636849, compound

Participants

Reaction Conditions

Reaction Steps

N-(4-Bromo-2-methyl-phenyl)-2,2,2-trifluoro-acetamide (described in example 4f) (4.9 g; 17.5 mmol), bis(pinacolato)diboron (6.66 g; 26.25 mmol), potassium acetate (5.15 g; 52.5 mmol) and bis(triphenylphosphine)palladium(II) dichloride (PdCl2(PPh3)2) (737 mg; 1.05 mmol) are suspended in dioxane (175 ml; dried over a molecular sieve), and four times the suspension is evacuated and ventilated with argon, with vigorous stirring. The mixture is then stirred at a bath temperature of 85° C. for 4 hours. After cooling to room temperature, the reaction mixture is concentrated and dimethoxyethane (10 ml), tetrakis-triphenylphosphine-palladium (1.21 g; 1.05 mmol), 5-(3-ethoxy-4-iodo-5-methoxymethoxy-benzyl)-pyrimidine-2,4-diamine (4.51 g; 10.5 mmol) and a 2 M aqueous sodium carbonate solution (70 ml) are added. The reaction mixture is stirred for approx. 25 hours under argon at 85° C. (bath temperature), cooled to room temperature and filtered with suction and the filtrate is concentrated. The residue obtained is dissolved in ethanol (210 ml), a 1 N aqueous sodium hydroxide solution is added and the mixture stirred is for 4½ hours in an oil bath of 50° C. The mixture is poured on to ice-water and extracted twice with ethyl acetate. The organic phases are washed with a saturated aqueous sodium chloride solution, dried over magnesium sulphate, filtered with suction and concentrated. The residue is chromatographed over silica gel (810 g) with methylene chloride/methanol/NH4OH 19/1/0.05. The red powder obtained (2.6 g) is suspended in methanol (100 ml), a 4.5 N aqueous hydrochloric acid (30 ml; 137 mmol) is added and the mixture is stirred for 45 minutes in an oil bath at 60° C. The methanol is evaporated, the residue is dissolved in water (200 ml) and the pH is adjusted to approx. 10 with NH4OH conc., while stirring. After stirring for 30 minutes at room temperature, the suspension is filtered with suction and the residue is washed with water and dried under a high vacuum. 2.20 g (33%) 4′-amino-4-(2,4-diamino-pyrimidin-5-ylmethyl)-6-ethoxy-3′-methyl-biphenyl-2-ol are obtained as a light-red powder.

Provenance & Evidence