Benzimidazole → HCID 11512174, compound

Participants

Reaction Steps

A solution of benzimidazole (9.2 mg) in anhydrous DMF (1.5 mL) under argon was cooled to 0-5° C. Sodium bis(trimethylsilyl)amide (0.6 M in toluene, 129 μL) was added via micropipette followed by (1-{2-[isopropyl(4-methoxyphenyl)amino]-2-oxoethyl}-5,7-dioxo-4-phenyl-4,5,6,7-tetrahydro-1H-1,4-diazepin-6-yl)methyl methanesulfonate (20 mg). After approximately 10 min., the reaction mixture was quenched with several drops of glacial acetic acid and evaporated in vacuo. The residue was partitioned between ethyl acetate and aqueous K2CO3 (5% w/v). The layers were separated and the aqueous layer was back-extracted with ethyl acetate. The combined organic layers were dried over anhydrous MgSO4, filtered and evaporated in vacuo. The residue was purified on a preparative TLC plate (20×20 cm, 500 □M) eluting with 5% methanol in CH2Cl2. The product band was removed, eluted with 4:1 CH2Cl2/methanol, filtered and evaporated in vacuo. The residue was lyophilized from CH3CN/H2O to provide 2-[6-(1H-benzimidazol-1-ylmethyl)-5,7-dioxo-4-phenyl-4,5,6,7-tetrahydro-1H-1,4-diazepin-1-yl]-N-isopropyl-N-(4-methoxyphenyl)acetamide as a white lyophilate (15 mg). 1H NMR (300 MHz, CDCl3) 1.13 (m, 6H), 3.86 (m, 1H), 3.90 (s, 3H), 3.97 (d, J=4 Hz, 2H), 4.90 (m, 1H), 5.07 (m, 2H), 5.90 (d, J=7 Hz, 1H), 5.99 (d, J=7 Hz, 1H), 7.01 (m, 2H), 7.18 (m, 2H), 7.33 (m, 8H), 7.85 (m, 1H), 8.26 (s, 1H).

Provenance & Evidence