Sodium hydride → 2-((5-Bromopyrimidin-2-yloxy)methyl)-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole

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Reaction Steps

A mixture of alcohol 101 (see Example 2M) (100 mg, 0.502 mmol) and 5-bromo-2-chloropyrimidine (156 mg, 0.806 mmol) in anhydrous DMF (2.5 mL) under N2 at 0° C. was treated with 60% NaH (32 mg, 0.80 mmol), then quickly degassed and resealed under N2. After stirring at room temperature for 140 min, the reaction was cooled (CO2/acetone), quenched with ice/aqueous NaHCO3 (10 mL), added to brine (40 mL), and extracted with CH2Cl2 (6×50 mL). The combined extracts were evaporated to dryness and the residue was chromatographed on silica gel. Elution with 0-0.25% MeOH/CH2Cl2 firstly gave foreruns, and then further elution with 0.25-0.5% MeOH/CH2Cl2 gave 2-{[(5-bromo-2-pyrimidinyl)oxy]methyl}-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole (103) (reported by Ding et al., WO 2009120789A1 from 101 via a similar procedure) (163 mg, 91%) as a cream solid: mp (MeOH/CH2Cl2/hexane) 224-226° C.; 1H NMR [(CD3)2SO] δ 8.77 (s, 2H), 8.14 (s, 1H), 4.61 (s, 2H), 4.41 (d, J=11.0 Hz, 1H), 4.20 (d, J=11.1 Hz, 1H), 1.70 (s, 3H). Anal. (C11H10BrN5O4) C, H, N.

Provenance & Evidence