4-Chloro-5-iodopyrimidine → 3'-[(5-Iodopyrimidin-4-yl)amino]-6-methylbiphenyl-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

3′-Amino-6-methylbiphenyl-3-carboxylic acid (3.00 g, 0.0132 mol) was mixed with 4-chloro-5-iodopyrimidine (3.30 g, 0.0137 mol) and isopropyl alcohol (60 mL). The resulting mixture was heated to 80° C., at which temperature solution occurred. A short time later, the product began to precipitate. After 2 h, HPLC showed 95% conversion of to product. HPLC Method: Zorbax SB C18, 5 μm, 15 cm, 35 C, flow 1.2 mL/min, 25% CH3CN—H20 (0.05% TFA), to 100% CH3CN in 8.0 min; stop time 11 min; detector 254 &220 nm; retention time starting material, 2.8 min (UVmax 205 & 230 nm); pyrimidine, 4.8 min (UVmax 240 & 270 nm); product, 4.9 min (UV max 204, 228, & 290 nm). The reaction was cooled to 20° C. The product was isolated by filtration, rinsed with iPrOH, then vacuum dried. Yield 5.35 g of a light tan powder. The product is believed to be the HCl salt or partial salt. 1H NMR (300 MHz, DMSO) δ 9.62 (br s, 1H, NH); 8.83 (s, 1H); 8.69 (s, 1H); 7.83 (dd, 1H); 7.76 (d, 1H); 7.42-7.58 (m, 4H); 7.25 (dt, 1H); 2.33 (s, 3H).

Provenance & Evidence