Ibudilast → Ibudilast

Participants

Reaction Steps

1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)-2-methylpropan-1-one. The dry salt (113 g) from Example 1 (a) was suspended in isobutyric anhydride (515 g) in a large round bottom flask equipped with a mechanical stirrer and K2CO3 (85 g) was added with stirring. The mixture was refluxed for 8 hours, cooled to room temperature and water (10 ml) was added followed by addition of K2CO3 (10 g) in portions. After the initial vigorous reaction subsided, water (500 ml) and ethyl acetate (500 ml) were added, followed by 280 g of K2CO3, added in portions with continuous mechanical stirring to control foaming. The reaction mixture was stirred for 1 hour at room temperature, 50 mL of 50% NaOH was added, and the mixture extracted with ethyl acetate (4×250 ml). Evaporation of the solution yielded a viscous oil, which was distilled under high vacuum to provide 25.2 g (32.9%) of 2-isopropylpyrazolo[1,5-a]pyridine (b.p. 45-75° C./0.25-0.5 mm Hg), and 60.4 g (51.3%) of 1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)-2-methylpropan-1-one (b.p. 125-135° C./0.1 mm Hg; m.p. 53-55° C.) (T. Irikura, et al., U.S. Pat. No. 3,850,941, Nov. 26, 1974). Compound 411.

Provenance & Evidence