4-Methoxyphenylacetic Acid → 2-(4-methoxyphenyl)-N-[6-(1H-pyrazol-4-yl)isoquinolin-3-yl]acetamide

Participants

Reaction Conditions

Reaction Steps

Activation of (4-Methoxy-phenyl)-acetic acid (315.6 mg, 1.9 mmol) is accomplished by treatment of the carboxylic acid in DMA (5 mL) with HATU (802.6 mg, 2.1 mmol) and triethylamine (388.2 mg, 3.8 mmol) at room temperature for 1 hour. The 6-(1H-Pyrazol-4-yl)-isoquinolin-3-ylamine (200.0 mg, 0.9 mmol) was added and the mixture was stirred at 75° C. for 24 hours. The reaction was monitored by LC/MS. Evaporation of DMA gave a residue that was washed with NaHCO3 to remove the by-products from HATU. The crude residue then was dissolved in MeOH (10 mL) and was treated with K2CO3 (26.0 mg, 0.5 mmol) at 75° C. for 18 hrs. The solvent was evaporated and the product extracted with CH2Cl2 (20 mL). The extracts were washed with water (3×10 mL) and evaporated. The crude product was purified by ISCO (with petroleum ether:ethyl acetate 50:50) to give the title compound as a light yellow crystalline solid product (143.3 mg, 41.4%). 1H NMR (DMSO-d6, 400 MHz): δ 3.68 (2H, s), 3.73 (3H, s), 6.79-6.98 (2H, m), 7.31 (2H, d, J=8.8 Hz,), 7.81 (1H, dd, J=8.6, 1.5 Hz,), 8.00 (1H, d, J=8.6 Hz), 8.08 (1H, s), 8.14 (1H, s), 8.41 (2H, d, J=8.3 Hz), 9.03 (1H, s), 10.69 (1H, s), 13.09 (1H, s). 13CNMR (DMSO-d6, 100 MHz): δ 42.18, 55.01, 106.30, 113.76, 120.44, 120.56, 124.11, 124.39, 126.71, 127.87, 128.06, 130.13, 135.26, 136.96, 137.87, 147.51, 150.75, 158.14, 170.14. HRMS: m/z 359.1489, calc. 359.1503. MS m/z, (APCI); 359.2 [(M+1)+100].

Provenance & Evidence