Reaction Steps
To a solution of (3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid, Example 15 (90 mg, 0.20 mmol) in N,N-dimethylformamide (1 mL) was added 1-hydroxybenzotriazole (43 mg, 0.32 mmol), triethylamine (0.06 mL, 0.40 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (103 mg, 0.32 mmol). The solution was stirred for twenty-five minutes followed by addition of ethanolamine (0.02 mL, 0.32 mmol). The solution was stirred for twenty hours at ambient temperature. The reaction was quenched with water and the resulting yellow solid was collected by vacuum filtration. Chromatography (reverse phase, acetonitrile/water) provided (3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-N-(2-hydroxyethyl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxamide (yellow solid, 30 mg, 33% yield). LC/MS on 4.6×50 mm C-18 column, tR=6.00 minutes (10 to 90% acetonitrile/water over 6 minutes at 2 mL/minute with detection 254 nm, at 50° C.); ES-MS m/z 463 (M+H); HRMS Calculated for C26H27ClN4O2: 463.1895 (M+H)+. Found: 463.1875; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.10-1.50 (m, 6H), 1.66-1.84 (m, 2H), 2.17-2.25 (m, 1H), 2.87-2.93 (m, 1H), 2.99-3.06 (m, 1H), 3.26-3.34 (m, 2H), 3.48 (t, J=6.18 Hz, 2H), 3.53-3.63 (m, 2H), 4.92 (dd, J=9.13, 6.18 Hz, 1H), 7.17 (dd, J=8.46, 1.75 Hz, 1H), 7.38 (d, J=2.15 Hz, 1H), 7.65 (d, J=8.86 Hz, 1H), 7.73 (d, J=8.59 Hz, 1H), 7.76 (s, 1H), 8.03 (d, J=8.06 Hz, 1H), 8.46 (t, J=6.31 Hz, 1H).
