Diisopropylethylamine → Ly-3031207

Participants

Reaction Conditions

Reaction Steps

To a thermally controlled reaction vessel, add 2-chloro-5-[(2,2-dimethylpropanoylamino)methyl]benzoic acid (420 g, 1.56 mol, 1.0 equiv), 2-aminoimidazole monosulfate (349 g, 1.87 mol, 1.2 equiv), N,N-dimethylformamide (2.94 L), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (722 g, 2.18 mol, 1.4 equiv), and N,N-diisopropylethylamine (869 mL, 4.98 mol, 3.2 equiv). Heat the resulting suspension to an internal temperature of 80° C. for 18 hours. Cool the reaction mixture to 10° C., pour the mixture into ice water (14 L), and stir for 90 min. Collect the solids by filtration, dry the material in air for 24 h, and in a vacuum oven at 50° C. for 24 h. Slurry the solid material in isopropanol (7 L), heat to an internal temperature of 73° C. for 3 h, and cool to 10° C. Filter the suspension to isolate the solid material. Dry the material in air for 24 h and in a vacuum oven at 55° C. for 48 h to give the title compound as an off-white solid (435 g, 83.4%). 1H NMR (DMSO-d6, 400 MHz): δ 11.84 (s, 2H), 8.13 (t, 1H, J=6.0 Hz), 7.47 (d, 1H, J=8.3 Hz), 7.40 (d, 1H, J=1.7 Hz), 7.31 (dd, 1H, J=8.3, 2.0 Hz), 6.73 (s, 2H), 4.27 (d, 2H, J=5.9 Hz), 1.12 (s, 9H). MS (m/z) (35Cl/37Cl) 335/337 (M+1).

Provenance & Evidence