4-Methylmorpholine → HCID 25107210, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of Example 24B (0.150 g, 0.470 mmol), 1,2-dihydrocyclobutabenzene-1-carboxylic acid (0.070 g, 0.470 mmol), N-methylmorpholine (0.103 mL, 0.940 mmol), and 1-hydroxybenzotriazole hydrate (0.080 g, 0.940 mmol) in N,N-dimethylformamide (2 mL) was added 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride (0.115 g, 0.589 mmol). The solution was heated to 50° C. for 3 h, cooled to room temperature, and partitioned between H2O (2 mL) and ethyl acetate (2 mL). The layers were separated, and the aqueous was extracted with additional ethyl acetate (2×2 mL). The combined organics were dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was dissolved in methanol (5 mL) and 2 N NaOH (0.50 mL) was added. After 5 h, the methanol was removed under reduced pressure. The aqueous was acidified with 10% HCl to pH 1. The solid was filtered and air-dried. Purification of the residue by RP-HPLC (preparative reversed-phase high pressure liquid chromatography) using a Zorbax SB-C18 7M 21.2×250 mm column with UV detection analyzed at 220 and 254 nM (preparative method: water with 0.1% trifluoroacetic acid and CH3CN with 0.1% trifluoroacetic acid gradient 5-95% CH3CN over 30 minutes at 15 mL/min) provided the title compound as a white-solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.67-1.94 (m, 2H), 2.39-2.47 (m, 4H), 3.31-3.40 (m, 2H), 3.93 (s, 2H), 4.44 (dd, J=4.9 and 2.9 Hz, 1H), 7.09-7.31 (m, 4H), 7.56-7.68 (m, 2H), 7.67-7.78 (m, 2H), 8.07 (s, 1H), 10.37 (s, 1H); MS (ESI) m/z 435 [M+H]+.

Provenance & Evidence