Cesium carbonate → (S)-7'-(6-chloropyridin-2-yloxy)-2'-(3,6-dihydro-2H-pyran-4-yl)-4'-fluoro-5H-spiro[oxazole-4,9'-xanthen]-2-amine

Participants

Reaction Conditions

Reaction Steps

A glass microwave reaction vessel was charged with 2-chloro-6-fluoropyridine (88 mg, 0.67 mmol), cesium carbonate (0.027 mL, 0.33 mmol) and (S)-2-amino-2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-5H-spiro[oxazole-4,9′-xanthen]-7′-ol (82 mg, 0.22 mmol, prepared as described in Method BB40 and Example 2 but using 4-bromo-2-fluorophenol and 2-bromo-5-methoxybenzoic acid) in DMF (0.8 mL). The reaction mixture was stirred and heated in a Initiator microwave reactor at 100° C. for 35 min. Then it was heated at 120° C. for 5 min. The crude material was purified by reverse-phase preparative HPLC using 0.1% TFA in CH3CN/H2O, gradient 35% to 65% to provide (S)-7′-(6-chloropyridin-2-yloxy)-2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-5H-spiro[oxazole-4,9′-xanthen]-2-amine (36 mg, 0.075 mmol, 33.7% yield) as a off-white solid.

Provenance & Evidence