1,4-Dioxane → HCID 50915115, compound

Participants

Reaction Steps

To a microwave vial equipped with a magnetic stirrer was added 2-chloro-5-(cyclopropylmethyl)-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (88 mg, 0.285 mmol), 1,4-dioxane (2 ml), 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (118 mg, 0.428 mmol), NaHCO3 (saturated, 0.491 mL), and PdCl2(dppf) (209 mg, 0.285 mmol). The reaction was irradiated in the microwave at 100° C. for 40 min. The reaction solution was then poured into water, extracted with ethyl acetate three times and the combined organic layers were washed with water and then brine, then dried with Na2SO4, filtered, and the filtrate concentrated in-vacuo to give a brown residue. The aqueous layer was acidified with AcOH (pH about 5) and concentrated in-vacuo to give a grey residue. The combined residues were purified via preparative LC/MS (45-50% gradient of 10 mmol NH4HCO3 in 20/80 (v/v) water/acetonitrile in 10 mmol NH4HCO3 in water, Phenomenex Gemini 5 μm C18, 75×30 mm column to give the title compound (54 mg, 0.128 mmol, 44.8% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.25-0.57 (m, 4 H) 1.18 (m, 1 H) 1.35 (s, 3 H) 2.62-2.71 (m, 3 H) 3.17-3.26 (m, 1 H) 3.54-3.65 (m, 1 H) 3.68 (d, J=11.62 Hz, 1 H) 3.81 (dd, J=14.53, 6.95 Hz, 1 H) 3.89-4.02 (m, 2 H) 4.07 (dd, J=11.62, 3.54 Hz, 1 H) 4.20 (dd, J=13.77, 2.40 Hz, 1 H) 6.07 (d, J=4.80 Hz, 1 H) 7.49 (d, J=8.84 Hz, 2 H) 8.19 (d, J=8.84 Hz, 2H) 8.36 (s, 1 H) 8.72 (s, 1 H). MS [M+H] found 423.

Provenance & Evidence