1,4-Dioxane → HCID 60164622, compound

Participants

Reaction Conditions

Reaction Steps

To a vial was added (E)-3-chloro-7-(2-fluoropyridin-3-yl)-6′,7′-dihydro-2′H-spiro[chromeno[2,3-c]pyridine-5,5′-[1,4]oxazepin]-3′-amine (50 mg, 0.122 mmol), potassium phosphate (78 mg, 0.365 mmol), 2-fluoropyridin-4-ylboronic acid (34.3 mg, 0.243 mmol), and 1,1-bis[(di-t-butyl-p-dimethylaminophenyl]palladium(ii) chloride (4.31 mg, 6.09 μmol), dioxane (609 μL) and water (203 μL). The reaction mixture was purged with N2 gas and heated at 100° C. in microwave reactor for 15 mins. It was diluted with water and extracted with EtOAc. The organic extract was washed with saturated NaCl aqueous solution, dried over MgSO4, filtered and concentrated in vacuo to give the crude material. The crude was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 25% to 40% to 80% DCM/MeOH (90/10) in DCM, to provide (R,E)-7-(2-fluoropyridin-3-yl)-3-(2-fluoropyridin-4-yl)-6′,7′-dihydro-2′H-spiro[chromeno[2,3-c]pyridine-5,5′-[1,4]oxazepin]-3′-amine as off-white solid. MS m/z=472.0. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.01-2.14 (m, 1 H) 2.24-2.41 (m, 1 H) 3.39 (dt, J=11.25, 5.62 Hz, 2 H) 4.37-4.47 (m, 1 H) 4.47-4.61 (m, 1 H) 6.13 (br. s., 2 H) 7.41 (d, J=8.31 Hz, 1 H) 7.50 (ddd, J=7.26, 5.01, 1.91 Hz, 1 H) 7.60 (dt, J=8.39, 1.87 Hz, 1 H) 7.67-7.75 (m, 2 H) 7.89-7.95 (m, 1 H) 8.03-8.16 (m, 2 H) 8.25 (dt, J=4.82, 1.50 Hz, 1 H) 8.38 (d, J=5.28 Hz, 1 H) 8.66-8.77 (m, 1 H).

Provenance & Evidence