Sodium hydride → HCID 66918801, compound

Participants

Reaction Steps

To a solution of N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-5-fluoro-2-nitrobenzamide (3.0 g) and (R)-(+)-1-(tert-butoxycarbonyl)-2-pyrrolidinemethanol (2.54 g) in DMF (45 ml) was added sodium hydride (1.54 g of a 60% dispersion in oil) portion-wise (ice bath cooling). The reaction was stirred for 43 hours at room temperature under an atmosphere of argon. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution (200 ml) and the resulting precipitate was collected by filtration, dissolved in methanol (10 ml) and 4N HCl in dioxane (5 ml) added. The reaction mixture was stirred at room temperature for 16 hours, concentrated and re-precipitated from methanol/ethyl acetate to yield N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-nitro-5-[(2R)-pyrrolidin-2-ylmethoxy]benzamide hydrochloride salt (3.32 g) as a yellow solid; NMR Spectrum: (DMSOd6) 0.64 (m, 2H), 0.75 (m, 2H), 1.83 (m, 1H), 1.95-2.12 (m, 2H), 2.21 (m, 1H), 2.37 s, 3H), 2.91 (m, 1H), 3.30 (m, 2H), 4.02 (m, 1M), 4.45 (m, 1H), 4.55 (m, 1H), 7.37 (m, 3H), 0.70 (d, 1H), 8.02 (s, 1H), 8.29 (d, 1M), 8.49 (d, 1H), 9.50 (s, 1H), 10.22 (s, 1H); Mass Spectrum: M+H+ 439.

Provenance & Evidence