4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → HCID 89462032, compound

Participants

Reaction Steps

The (S)-2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthene]-2,7′-diamine (0.048 g, 0.126 mmol) was suspended in MeOH (2.5 mL). The 5-methoxypyrazine-2-carboxylic acid (0.019 g, 0.126 mmol) was added, followed by 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride (0.035 g, 0.126 mmol). After 30 min another 1 mg of the acid (0.05 equiv) and 1.75 mg of the coupling agent (0.05 equiv) were added. After 2 h, the reaction was quenched with 15 mL of half-saturated NaHCO3. The material was extracted with 5% MeOH-dcm (3×25 mL). The organics were combined, washed with dilute brine (8 mL), dried over MgSO4 and concentrated. The material was purified through silica gel (35 mL) using 10% to 20% EtOH in 2:1 hexane-EtOAc, affording (S)—N-(2-amino-2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-7′-yl)-5-methoxypyrazine-2-carboxamide (35 mg, 0.067 mmol). MS m/z=518 [M+H]−1. 1H NMR in CDCl3 δ: 9.52 (s, 1H), 9.03 (s, 1H), 8.16 (s, 1H), 7.76 (dd, 1H, J=8.7, 2.4), 7.66 (d, 1H, J=2.5), 7.01 (s, 1H), 6.96 (dd, 1H, J=11.3, 1.8), 4.20-4.40 (m, 6H), 4.07 (s, 3H), 3.53 (m, 2H), 2.80 (m, 1H), 1.75-1.90 (m, 4H).

Provenance & Evidence