1-Hydroxybenzotriazole → HCID 16666598, compound

Participants

Reaction Steps

To a solution of 4-{(3R)-3-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]-1,3′-bipyrrolidin-1′-yl}benzoic acid (35 mg, 0.069 mmol), HATU (0.032 g, 0.086 mmol), N,N-diisopropylethylamine (30.2 μL, 0.173 mmol), 1-Hydroxybenzotriazole (11.7 mg, 0.0867 mmol) in DMF (3.0 mL) was added diethylame (8.25 μL, 0.079 mmol). The reaction mixture was allowed to stir at room temperature overnight. To the mixture was added NaHCO3 (sat. aq., 10 mL) and dichloromethane (10 mL). The organic layer was separated and the aqueous layer was washed with an addition portion of dichloromethane (10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The resulting crude product was subjected to flash chromatography (15% MeOH, 1% NH4OH in EtOAc) to afford, as a mixture of diastereomers, N,N-diethyl-4-{(3R)-3-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]-1,3′-bipyrrolidin-1′-yl}benzamide (32 mg, 82%) as a white solid. 1H-NMR (MeOD) δ: 1.19 (t, J=6.6 Hz, 6H), 1.66-1.80 (m, 1H), 1.90-2.05 (m, 1H), 2.18-2.40 (m, 2H), 2.50-2.70 (m, 2H), 2.80-3.06 (m, 4H), 3.15-3.40 (m, 4H), 3.38-3.60 (m, 5H), 4.03 (s, 2H), 4.37-4.50 (m, 1H), 6.58 (d, J=8.4 Hz, 2H), 7.26 (d, J=8.1 Hz, 2H), 7.69 (t, J=7.2 Hz, 1H), 7.86 (d, J=7.2 Hz, 1H), 8.14 (d, J=7.5 Hz, 1H), 8.22 (s, 1H). MS m/z: 560 (M+1)

Provenance & Evidence