Potassium Phosphate, Tribasic → HCID 60164406, compound

Participants

Reaction Conditions

Reaction Steps

A vial was charged with (E)-3-chloro-7-(2-fluoropyridin-3-yl)-6′,7′-dihydro-2′H-spiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazepin]-5′-amine (142 mg, 0.346 mmol), 2-fluoropyridin-4-ylboronic acid (122 mg, 0.864 mmol), Pd(AmPhos)2Cl2 (12.24 mg, 0.017 mmol), and potassium phosphate (220 mg, 1.037 mmol). The vial was flushed with Ar (g), then dioxane (1296 μL) and water (432 μL) were added in sequence. The vial was sealed and heated in a microwave reactor for 30 min at 110° C. The mixture was extracted with EtOAc (3×), and the combined organic extracts were concentrated. The crude product was purified by chromatography on silica gel (10-100% of a 90:10:1 mixture of DCM/MeOH/NH4OH in DCM) to give (E)-7-(2-fluoropyridin-3-yl)-3-(2-fluoropyridin-4-yl)-6′,7′-dihydro-2′H-spiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazepin]-5′-amine as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=8.71 (d, J=0.4 Hz, 1 H), 8.38 (d, J=5.3 Hz, 1 H), 8.26 (td, J=1.5, 4.8 Hz, 1 H), 8.13 (ddd, J=1.9, 7.5, 10.4 Hz, 1 H), 8.07 (s, 1 H), 7.95 (td, J=1.8, 5.2 Hz, 1 H), 7.72 (s, 1 H), 7.69-7.59 (m, 2 H), 7.50 (ddd, J=1.9, 4.9, 7.4 Hz, 1 H), 7.42 (d, J=8.6 Hz, 1 H), 6.16 (br. s., 2 H), 3.86 (t, J=5.6 Hz, 2 H), 3.72 (q, J=12.8 Hz, 2 H), 3.09-2.90 (m, 2 H). MS m/z=472.0. Calc'd for C26H20F2N5O2: 472.2. The racemic material (104 mg) was subjected to chiral SFC separation, using 35% MeOH with diethylamine to afford 45 mg of the (R)-enantiomer (peak 1) and 44 mg of the (S)-enantiomer (peak 2) as white solids.

Provenance & Evidence