4-Methylmorpholine → HCID 58806160, compound

Participants

Reaction Conditions

Reaction Steps

To a cooled solution (0° C.) of 3-[4-[(2,4-difluorobenzyl)oxy]-5-ethyl-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoic acid (from Step 4) (0.25 g, 0.62 mmol) and 4-methylmorpholine (0.10 mL, 0.94 mmol) in DMA (2 mL) was added isobutyl chloroformate (0.12 mL, 0.94 mmol). Stirred 5 min at 0° C., 30 min at ambient temperature. Added (R)-(−)-2-amino-1-propanol (0.07 mL, 0.94 mmol) and DMAP (0.02 g, 0.12 mmol) to the cooled (0° C.) reaction mixture. Stirred at ambient temperature for 3 h. Purified crude product by preparatory HPLC using a 10-90% CH3CN/H2O (30 min) gradient containing 0.5% TFA at a flow rate of 80 mL/min. Appropriate fractions (M+H m/z=458) were combined and concentrated to approximately 20 mL under reduced pressure. Added 5% NaHCO3 (20 mL) and extracted with DCM (3×15 mL). The organic extracts were dried over Na2SO4, filtered, concentrated under reduced pressure, and dried in vacuo to give the desired product as an off-white foam (0.20 g, 70%). 1H NMR (CD3OD/400 MHz) δ8.18 (s, 1H), 7.90 (m, 1H), 7.73 (m, 1H), 7.57 (q, 1H, J=8.4 Hz), 7.50 (d, 1H, J=8.0 Hz), 7.01 (m, 2H), 5.52 (q, 2H, J=12.4 Hz), 4.16 (m, 1H), 3.57 (m, 2H), 2.21 (q, 2H, J=7.6 Hz), 2.17 (s, 3H), 1.22 (m, 3H), 1.05 (t, 3H, J=7.2 Hz). ESHRMS m/z 458.1855 (M+H calculated for C24H26F2N3O4 requires 458.1886).

Provenance & Evidence