Triethylamine → 5-[(1R)-1-{7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyrazine-2-carboxamide

Participants

Reaction Steps

To a solution of 5-[(R)-1-(2,7-diaza-spiro[3.5]non-2-yl)-indan-5-yl]-pyrazine-2-carboxylic acid amide (10-1c, 28 mg, 0.08 mmol) in 3 mL of DMF was added (5-methoxy-pyridin-2-yl)-acetic acid (SM-1aa, 13.0 mg, 0.08 mmol), HBTU (33.0 mg, 0.09 mmol) and triethylamine (0.06 mL, 0.46 mmol). The solution was stirred at room temperature overnight. The reaction was concentrated under reduced pressure and coevaporated with toluene. The residue was partitioned between 10 mL of dichloromethane and 10 mL of 1N NaOH solution. The organic layer was washed with saturated brine, dried over Na2SO4 and concentrated. The crude product was purified by Biotage reverse phase column chromatography (Biotage, Inc.) using 100-60% water in acetonitrile to give the desired product 12.0 mg (27%). MS (ES+) 513.4 (M+H)+. 1H NMR (CD3OD) δ 1.56-1.81 (m, 4H), 1.81-2.09 (m, 1H), 2.11-2.35 (m, 1H), 2.93 (d, 1H), 3.12 (d, 1H), 3.20-3.27 (m, 2H), 3.31-3.41 (m, 1H), 3.43-3.66 (m, 4H), 3.69-3.89 (m, 5H), 4.06 (dd, 1H), 4.54-4.81 (m, 2H), 7.25 (d, 1H), 7.34 (dd, 1H), 7.50 (d, 1H), 7.97 (dd, 1H), 8.04 (s, 1H), 8.13 (d, 1H), 9.12 (d, 1H), 9.22 (d, 1H).

Provenance & Evidence