Ammonia → CID 46780499

To a saturated solution of methanolic ammonia (12 ml) at room temperature was added artemisinin (1.128 g, 4 mmol). The solution was stirred for 1.5 hours and concentrated under reduced pressure to give a light yellow solid. The solid was dissolved in dichloromethane (180 ml), and 2,6-di-tert-butyl-4-methylphenol (BHT) (80 mg, 0.36 mmol), 15% sulphuric acid (0.8 ml), and silica gel (8.0 g) were added in succession. After stirring overnight at room temperature, the reaction mixture was filtered and the silica gel washed with dichloromethane. The combined organic solution and washes were concentrated under reduced pressure. Column chromatography of the residue on silica gel with acetone:dichloromethane (8:92) gave crystalline solid 11-azaartemisinin (510 mg, 45%): mp 143-145° C.; Rf=0.40 (acetone:CH2Cl2, 15:85); [α]25D=−40.9° (c 0.127, CH2Cl2); IR 3313, 3223, 2928, 2873, 1668 cm−1; CIMS (NH3) 299 (M+NH4+, 76), 282 (M+1,100); 1H NMR δ 0.93-1.01 (2H, m), 0.93 (3H, d, J=5.5 Hz), 1.07 (3H, d, J=7.2 Hz), 1.30 (3H, s), 1.25-1.42 (3H, m), 1.61-1.70 (2H, m), 1.71-1.77 (1H, m), 1.92 (2H, dm, J=10.2 Hz), 2.34 (1H, m), 3.17 (1H, pent, J=6.8 Hz), 5.33 (1H, s), 5.93 (1H, bs).

1. concentrationconcentrated under reduced pressure
2. customto give a light yellow solid
3. stirringAfter stirring overnight at room temperature
4. filtrationthe reaction mixture was filtered
5. washthe silica gel washed with dichloromethane
6. concentrationThe combined organic solution and washes were concentrated under reduced pressure

ORD record

ord-0d37e54e0a4f4aee9c3853f9e24bf17f

Source dataset

uspto-grants-2003_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06649647B1