Trifluoroacetic acid → Trifluoroacetic acid

Participants

Reaction Steps

2-(4-Nitrophenyl)ethyl 3-[(tert-butyl)oxycarbonyl]pyrrolo[4,5-e]indoline-7-carboxylate (1.62 g) (Compound 1-1 of Scheme I) was selectively deprotected by treatment with 15 mL of trifluoroacetic acid (i.e., TFA) for 1 h. TFA was evaporated to afford a TFA salt of amine 12. Residual TFA was removed by co-evaporation with ether followed by drying under vacuum. The TEA salt was dissolved in 30 mL of anhydrous DMF in the presence of 0.9 mL of triethylamine. Compound 1-2 of Scheme II (see Example 1) (1.86 g) was added and the reaction was stirred at room temperature overnight. The solvent was evaporated under vacuum and the semi-solid residue was triturated with 10% MeOH/dichloromethane. The resulting yellow solid was collected by filtration and washed with the MeOH/dichloromethane mixture followed by ether. Drying under vacuum afforded 2.2 g of the dimer 13. The product contained about 1 equivalent of DMF according to the NMR analysis. 1H MNR (d6-DMSO) δ: 11.96 (s, 1H, NH), 10.27 (s, 1H, NH), 8.84 (br s, 1H), 8.33 (d, J=8.8 Hz, 1H), 8.19 (d, J=8.8 Hz, 2:H), 8.12 (br s, 1H), 7.65 (d, J=8.8 Hz, 2H), 7.35 (d, J=8.8 Hz, 1H), 7.08 (s, 1H), 7.07 (s, 1H), 4.64 (t, J=8 Hz, 2H), 4.57 (t, J=6.4 Hz, 2H), 4.03 (t, J=8.5 Hz, 2H), 3.44 (t, J=8 Hz, 2H), 3.27 (t, J=8.5 Hz, 2H), 3.22 (t, J=6.6 Hz, 2H), 3.09 (m, 6H), 1.52 (s, 9H) and 1.16 (t, J=7.4 Hz, 9H).

Provenance & Evidence