4-Methylmorpholine → HCID 89906211, compound

Participants

Reaction Conditions

Reaction Steps

Into a solution of (R)-3-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-6-iodopyrimidin-5-yl)butanoic acid (100 g, 210 mmol) in tetrahydrofuran (700 mL) was added 1,1′-carbonyldiimidazole (40.9 g, 252 mmol) in portions. The reaction mixture was stirred at 20° C. for 1 h and cooled to 5° C. N,O-dimethylhydroxyamine hydrochloride (41.0 g, 420 mmol) was added in portions followed by N-methylmorpholine (6.94 mL, 63.0 mmol). The mixture was stirred at 5° C. for about 1 h, slowly warmed up to room temperature, and stirred for 24 h. Saturated aqueous ammonium chloride (500 mL) and water (150 mL) were added to get a clear phase separation. The organic layer was washed with saturated aqueous ammonium chloride (500 mL) and brine (200 mL). The residual water was azeotroped off to less than 500 ppm by co-evaporation with tetrahydrofuran. The product, as a solution in tetrahydrofuran was used for the next step without further purification or isolation (weight assay yield: >99%. 1H NMR (300 MHz, CDCl3) δ 8.23 (s, 1H), 3.84 (ddq, J=9.0, 7.2, 5.1 Hz, 1H), 3.72 (s, 3H), 3.61-3.57 (m, 4H), 3.42 (dd, J=16.5, 9.0 Hz, 1H), 3.25-3.21 (m, 4H), 3.17 (s, 3H), 2.76 (dd, J=16.5, 5.1 Hz, 1H), 1.47 (s, 9H), 1.47 (d, J=7.2 Hz, 3H). HRMS calcd. For C19H31IN5O4 [M+H]+: 520.1415. found 520.1413.

Provenance & Evidence