Benzylamine → [4-(3,3-Dimethyl-ureido)-6,8-dimethoxy-isoquinolin-1-ylmethyl]-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A stirred solution of 1-(tert-butoxycarbonylamino-methyl)-6,8-dimethoxy-isoquinoline-4-carboxylic acid (115 mg, 0.317 mmol) in 8 mL of dioxane, at room temperature, was treated with 49 mg (0.380 mmol, 1.2 eq) diisopropylethyl amine and allowed to stir for 5 minutes. Diphenylphosphoryl azide (96 mg, 1.02 eq) was added dropwise and the reaction was heated to 95° C. After 30 minutes, the reaction was removed from heat, and 46 mg (0.380 1.2 eq) of N-methyl, N-benzylamine was added. The reaction was then heated at 75° C. for 4 h. After cooling to room temperature, the solution was diluted with 15 mL of EtOAc, and was washed sequentially with water, then 1% NH4OH, then brine. The organic phase was dried over MgSO4, filtered through a plug of silica and concentrated. The product was purified by flash chromatography, eluting with 1% MeOH in DCM, to give 101 mg, 66% of the desired urea, as white solid. H1-NMR (CDCl3): δ 8.35 (s, 1H), 7.3-7.4 (m, 5H), 6.77 (s, 1H), 6.45 (s, 1H), 6.34 (s, 1H), 6.30 (s, 1H), 4.94 (d, J=4.7 Hz, 2H), 4.65 (s, 2H), 3.92 (s, 3H), 3.71 (s, 3H), 3.15 (s, 3H), 1.51 (s, 9H). MS: APCI (M+H) calc'd for C26H32N4O5+H=481.6; found 481.0.

Provenance & Evidence