Potassium bis(trimethylsilyl)amide → N-benzyl-2-(8,9-difluoro-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-N-isopropyl-acetamide

Participants

Reaction Conditions

Reaction Steps

To a solution of KHMDS (0.5 M in THF, 16.6 mL, 8.33 mmol) at 0° C. was added 8,9-difluoro-1-phenyl-4H,6H-2,3,6,10b-tetraaza-benzo[e]azulen-5-one (Preparation 4(C) (2.0 g, 6.4 mmol) in DMF (20 mL). The reaction was stirred at 0° C. for 35 minutes, was cooled to −10° C., and a solution of N-benzyl-2-bromo-N-isopropyl-acetamide (Preparation 1(C) (1.9 g, 7.0 mmol) in DMF (20 mL) was added. The reaction was stirred at −10° C. for 2 hours and at room temperature for 24 hours. The reaction was quenched with a pH 6.8 buffer and the aqueous solution was washed with EtOAc (3×). The combined organic solutions were washed with brine (4×), dried (Na2SO4), filtered and concentrated. Purification by medium pressure chromatography eluting with a solvent gradient (CH2Cl2 to 3% MeOH in CH2Cl2) provided 2.01 g of N-benzyl-2-(8,9-difluoro-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-N-isopropyl-acetamide. 1H NMR (CD2Cl2) δ 7.60-7.17 (m, 11H), 6.75 (q, 1H), 4.85-4.38 (m, 4H), 4.10 (q, 1H), 3.60 (q, 1H), 3.41 (s, 1H), 1.21 (q, 3H), 1.13 (q, 3H); MS 502.4 (M+1), 500.3 (M−1).

Provenance & Evidence