Water → (S)-7-(2-fluoropyridin-3-yl)-3-(2-fluoropyridin-4-yl)-5',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazin]-2'-amine

Participants

Reaction Conditions

Reaction Steps

In a microwave vial, potassium phosphate (0.084 g, 0.394 mmol), PdCl2(AmPhos)2 (8.38 mg, 0.012 mmol), and 2-fluoropyridin-4-ylboronic acid (0.024 g, 0.171 mmol) were loaded. The (S)-3-bromo-7-(2-fluoropyridin-3-yl)-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-2′-amine (0.058 g, 0.131 mmol) was added as a solution in dioxane (2.5 mL). Water (1 mL) was added and argon gas was blown through the vessel, which was sealed and heated in a 90° C. oil bath for 1.5 h. The residue was taken up in 5% MeOH/DCM (60 mL) and the organic layer was extracted with dilute brine (2×6 mL), then was dried over sodium sulfate and concentrated. The residue was purified by chromatography (4.5-5.5% MeOH/DCM) to afford (S)-7-(2-fluoropyridin-3-yl)-3-(2-fluoropyridin-4-yl)-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-2′-amine (Example 60A; 44 mg). MS (m/z) 458 (M+H)+. 1H NMR (400 MHz, CDCl3) δppm: 8.57 (d, 1 H, J=2.5 Hz), 8.32 (d, 1 H, J=5.3 Hz), 8.22 (d, 1 H, J=4.7 Hz), 8.07 (d, 1 H, J=2.3 Hz), 7.88 (m, 1 H), 7.55 (m, 2 H), 7.43 (m, 2 H), 7.30 (m, 1 H), 7.17 (s, 1 H), 4.39 (br, 2 H), 4.18 (m, 2 H), 2.02 (m, 1 H), 1.90 (m, 1 H).

Provenance & Evidence