Tri-o-tolylphosphine → 4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)benzoic acid

Participants

Reaction Conditions

Reaction Steps

tri-o-Tolylphosphine (18 mg, 0.060 mmol) was stirred in DMF (3 mL). The mixture was degassed by bubbling nitrogen through it until all additions were complete. To the mixture was added palladium acetate (6.8 mg, 0.030 mmol), and the resulting mixture was stirred at 20° C. for 5 min. To this mixture was added sodium acetate (37.1 mg, 0.452 mmol) and 3′-[(5-iodopyrimidin-4-yl)amino]-6-methylbiphenyl-3-carboxylic acid (0.13 g, 0.30 mmol). The resulting mixture was heated to reflux for 2 h. LCMS showed complete reaction to give the desired product, M+H 304; and a small amount of reduction product (M+H 306). The mixture was cooled to 20° C. The product was isolated by prep HPLC/MS using a 30 mm×100 mm C18 column; 25% CH3CN—H2O (0.1% TFA), 1.75 min, to 40% at 6 min; 60 mL/min; detector set at m/z 304; retention time, 3.2 min; reduction product, 4.3 min. The HPLC fractions were freeze dried to yield 45 mg of the TFA salt, a white solid. 1H NMR (d6-DMSO) δ 13.0 (br s, 1H, NH); 9.6 (s, 1H); 9.1 (s, 1H); 8.3 (d, 1H); 7.8 (m, 2H); 7.5 (s, 1H); 7.4 (m, 2H); 2.3 (s, 3H).

Provenance & Evidence