Potassium Carbonate → 1-(4-(3,4-dichlorophenyl)piperazin-1-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

Participants

Reaction Conditions

Reaction Steps

1-Chloro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (from Example 73, step 2; 0.050 g, 0.153 mmol) and potassium carbonate (0.106 g, 0.767 mmol) were dissolved in DMF (1.023 ml). 1-(3,4-dichlorophenyl)piperazine (0.071 g, 0.307 mmol) was added and the reaction was stirred overnight at 120° C. The reaction was filtered through a syringe filter and purified via HPLC (Phenominex C18 column, 150×30 mm, 5 micron; gradient elution 25 to 70% MeCN:H2O with 0.1% TFA modifier). The product fractions were concentrated and passed through a SCX ion exchange column (pre-wetted with methanol). The column was flushed several times with methanol, then the product was liberated by flushing the column several times with 2.0 M ammonia in methanol. The product-containing filtrate was concentrated to afford 1-(4-(3,4-dichlorophenyl)piperazin-1-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=8.40 (d, J=1.8 Hz, 1H), 8.28 (d, J=8.9 Hz, 1H), 8.23 (d, J=5.7 Hz, 1H), 7.88 (dd, J=1.9, 8.8 Hz, 1H), 7.63 (d, J=5.8 Hz, 1H), 7.44 (d, J=9.0 Hz, 1H), 7.28 (d, J=4.6 Hz, 1H), 7.22 (d, J=2.9 Hz, 1H), 7.02 (dd, J=2.8, 9.1 Hz, 1H), 6.87 (d, J=4.6 Hz, 1H), 3.46 (s, 8H). m/z (ESI) 521.1 (M+H)+.

Provenance & Evidence