Diisopropylethylamine → (Z)-[4-[3-[2,3-dihydro-2-oxo-3-[(1H-pyrrol-2-yl)methylene]-1H-indol-4-yl]-phenylcarbamoyl]-cyclohexyl]-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A suspension of (Z)-4-(3-aminophenyl)-1,3-dihydro-3-[(1H-pyrrol-2-yl)methylene)]-2H-indol-2-one hydrochloride (53 mg, 0.157 mmol) (from Example 5 supra) and 4-(tert-butoxycarbonylamino)cyclohexanecarboxylic acid (53 mg, 0.204 mmol) (prepared according to K. J. Cutrona et al., Tetrahedron Lett. 37(29):5045-5048 (1996)) in 4 mL of dry N,N-dimethylformamide was treated with O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU, 77 mg, 0.204 mmol) (Advance ChemTech) and N,N-diisopropylethylamine (88 μL , 0.628 mmol) (Aldrich). The reaction mixture was heated at 60° C. under a nitrogen atmosphere for 15 h. The reaction mixture was then diluted with 20 mL of a 1N aqueous hydrochloric acid solution and extracted with ethyl acetate (3×20 mL). The combined organic extracts were concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 45% ethyl acetate-hexanes elution) provided pure (Z)-[4-[3-[2,3-dihydro-2-oxo-3-[(1H-pyrrol-2-yl)methylene]-1H-indol-4-yl]-phenylcarbamoyl]-cyclohexyl]-carbamic acid tert-butyl ester (51.4 mg, 62%) as a yellow solid.

Provenance & Evidence