Hydrochloric Acid → HCID 51352115, compound

Participants

Reaction Conditions

Reaction Steps

To crude 2-(2-chloro-6a-methyl-6-oxo-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)-2-methylpropanoic acid (79 mg, about 0.233 mmol, as a mixture with its methylester) was added 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (0.077 g, 0.28 mmol), Pd(dppf)C12-dichloromethane, 1,4-dioxane (3 mL) and NaHCO3 (sat., 1.5 mL). It was heated under an air-filled balloon (1 atm) at 100° C. (bath temperature) for 1.5 hours and then LiOH.H2O (100 mg) was added and heated continued at 80° C. (bath temperature) for 1 hour and 40 minutes The mixture was diluted with water and MeOH, passed through a microfilter. The filtrate was acidified with concentrated HCl (0.1 mL) to pH<7 and then purified on the HPLC (20-20% of AcCN [containing 0.035% TFA] in water [containing 0.05% TFA], Phenomenex Gemini 5 μm C18, 75×30 mm column) to give 2-methyl-2-(6a-methyl-2-(4-(3-methylureido)phenyl)-6-oxo-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)propanoic acid as a clear semisolid (10.2 mg). 1H NMR (400 MHz, METHANOL-d6) δ ppm 1.55 (s, 3H) 1.68 (s, 3H) 1.81 (s, 3H) 2.80 (s, 3H) 3.49 (m, 1H) 3.69 (dd, J=12, 4 Hz, 1H) 3.74 (d, J=12 Hz, 1H) 4.05 (d, J=12 Hz, 1H) 4.15 (dd, J=12, 4 Hz, 1H) 4.48 (d, J=12 Hz, 1H) 7.62 (d, J=8 Hz, 2H) 8.10 (s, 1H) 8.14 (d, J=8 Hz, 2H). MS [M+H] found 455.4.

Provenance & Evidence