5-Fluoro-3-pyridinamine → HCID 59548269, compound

Participants

Reaction Steps

A solution of 4-(2-chloro-5-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (85 mg, 0.355 mmol) and 3-amino-5-fluoropyridine (118 mg, 1.053 mmol) in THF (3 mL) was cooled in an ice bath under nitrogen. After 5 min, a solution of LiHMDS (1 M in THF, 2500 μL, 2.500 mmol) was added. After 10 min, the cooling bath was removed. After 2 h, HCl (5 N, 0.5 mL) was added. EtOAc (10 mL) and saturated NH4Cl (10 mL) were added. The mixture was vigorously stirred for 15 min. The resulting emulsion was filtered through a glass frit. The collected solid was dissolved in warm DMSO and purified by prep HPLC (30-75% MeCN/water/w 0.1% TFA over 20 min). The collected product fractions were concentrated to dryness. Saturated NaHCO3 (10 mL) was added. The mixture was neutralized with HCl (5N) and filtered. The filtrate was extracted with iPrOH (5%) in CHCl3 (3×5 mL). The combined organic layers were dried over Na2SO4 and concentrated to a yellow solid which was filtered as a suspension in ether to give the product as a yellow powder (18 mg). LCMS (ES, pos.): calcd for C14H11F2N7: 315.1. found: 316.1 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.18 (s, 1H); 8.82 (s, 1H); 8.62 (dd, J=9.78, 3.13 Hz, 1H); 8.44-8.53 (m, 2H); 8.18 (d, J=2.54 Hz, 1H); 8.04 (br. s., 1H); 7.90 (br. s., 1H); 2.46 (s, 3H). 19F NMR (377 MHz, d6-DMSO) δ −139.21 (s, 1F); −127.41 (s, 1F).

Provenance & Evidence