1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 68312971, compound

Participants

Reaction Steps

To a suspension of 2-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-yloxy]-2-methylpropionic acid from Example 45 (0.0922 mmol) in DMF (2 mL) were added DIPEA (47 ul, 0.277 mmol), 1-methylpiperazine (31 uL, 0.277 mmol), HOBt (19 mg, 0.138 mmol) and EDCI (27 mg, 0.138 mmol) and the reaction mixture was stirred at RT for 2 h. Additional EDCI (50 mg) was added and the reaction mixture was stirred at RT for 18 h. The mixture was then partitioned between EtOAc and water. The aqueous layer was further extracted with EtOAc and the combined organic layers were washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-8% MeOH in DCM) affording 250 as a white solid (28 mg, 60% over three steps). LCMS: RT 2.92 min [M+H]+ 494.1. 1H NMR (DMSO, 400 MHz): δ 8.29 (1H, d, J=8.97 Hz), 7.83 (1H, s), 6.64 (1H, dd, J=8.98, 2.60 Hz), 6.42 (1H, d, J=2.57 Hz), 5.88-5.76 (1H, m), 4.47 (4H, s), 3.75-3.44 (4H, m), 2.24 (3H, s), 2.19 (2H, s), 2.06-1.94 (5H, m), 1.58 (6H, s), 1.44 (6H, d, J=6.59 Hz)

Provenance & Evidence