Potassium Carbonate → 1-(3-phenylpyrrolidin-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). 3-Phenyl-pyrrolidine (0.032 ml, 0.230 mmol) was added and the reaction was stirred overnight at 110° C. The reaction was filtered through a syringe filter and purified via HPLC (25 to 70% MeCN:H2O with 0.1% TFA modifier). The product fractions were combined and concentrated. The material was dissolved in methanol and passed through an SCX ion exchange column (pre-wetted with methanol). The column was flushed with methanol, then the product was liberated by flushing the column with 2 M ammonia in methanol. The filtrate was combined to afford 1-(3-phenylpyrrolidin-1-yl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=8.34 (d, J=8.9 Hz, 1H), 8.16 (d, J=1.9 Hz, 1H), 8.00 (d, J=5.6 Hz, 1H), 7.71 (dd, J=1.9, 8.9 Hz, 1H), 7.40-7.31 (m, 4H), 7.28-7.22 (m, 1H), 7.19 (d, J=5.6 Hz, 1H), 7.11 (d, J=4.2 Hz, 1H), 6.67 (d, J=4.3 Hz, 1H), 4.12-3.97 (m, 2H), 3.94-3.77 (m, 2H), 3.55-3.42 (m, 1H), 2.42-2.27 (m, 1H), 2.19-2.04 (m, 1H). m/z (ESI) 437.2 (M+H)+.

Provenance & Evidence