2-Chloro-4-methoxypyrimidine → tert-Butyl [3-(4-methoxypyrimidin-2-yl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]acetate

Temperature

130 °C

A mixture of tert-butyl (2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)acetate (200 mg, 0.806 mmol, described in Intermediate 4) and sodium bis(trimethylsilyl)amide (1.0 M in THF, 1.69 mL, 1.69 mmol) in THF (0.5 mL) was stirred for 5 min, then 2-chloro-4-methoxypyrimidine (583 mg, 4.03 mmol) was added and argon was bubbled through the mixture for 5 min. The reaction mixture was heated at 130° C. for 10 min in a microwave reactor. The cooled mixture was partitioned between CHCl3 (10 mL) and saturated aqueous NaHCO3 (5 mL). The aqueous phase was extracted further with CHCl3 (10 mL), and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane::EtOAc—100:0 to 80:20, to give the title compound. MS: m/z=357 (M+1).

1. customargon was bubbled through the mixture for 5 min
2. customThe cooled mixture was partitioned between CHCl3 (10 mL) and saturated aqueous NaHCO3 (5 mL)
3. extractionThe aqueous phase was extracted further with CHCl3 (10 mL)
4. dry with materialthe combined organic layers were dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe crude product was purified by silica gel chromatography
8. washeluting with a gradient of hexane

ORD record

ord-dd3486115a3c4d4ebaa7998819f6d400

Source dataset

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07202251B2