Thionyl Chloride → 6-[(2-{[(3R)-3-methoxypyrrolidin-1-yl]carbonyl}thieno[3,2-b]pyridin-7-yl)oxy]-2-methylbenzo[b]thiophene-3-carboxylic acid cyclopropylamide

Participants

Reaction Steps

Thionyl chloride (31 μl, 0.427 mmole) was added to a suspension of 6-[(2-{[(3R)-3-methoxypyrrolidin-1-yl]carbonyl}thieno[3,2-b]pyridin-7-yl)oxy]-2-methylbenzo[b]thiophene-3-carboxylic acid 11c (40 mg, 0.085 mmole) in dichloroethane (1 ml). The reaction mixture was heated to reflux for 90 minutes, cooled to room temperature, and concentrated in vacuo. The yellow residue was dissolved in CH2Cl2 (1 ml) and cyclopropylamine (30 μl, 0.427 mmole) was added. The resulting mixture was stirred at ambient temperature for 16 hours, diluted with CH2Cl2 (10 ml), and washed with H2O (5 ml). The aqueous layer was extracted with CH2Cl2 (2×5 ml) and the combined organics were dried (Na2SO4), filtered, and concentrated in vacuo. The crude mixture was purified by silica gel chromatography (5% MeOH/EtOAc) to afford 20 mg (46%) of a pale yellow solid. 1H NMR (DMSO-d6, 300 MHz) δ8.58 (1H, d, J=5.3 Hz), 8.46 (1H, d, J=4.5 Hz), 8.06 (1H, s) 7.96 (1H, d, J=2.3 Hz), 7.81 (1H, J=8.7 Hz), 7.32 (1H, dd, J=2.3, 8.7 Hz), 6.75 (1H, d, J=5.3 Hz), 4.10-3.82 (4H, m), 3.61 (2H, m), 3.27, 3.24 (3H, s), 2.91 (1H, m), 2.72 (1H, m), 2.57 (3H, s), 0.76-0.70 (2H, m), 0.50-0.55 (2H, m). Anal. Calcd. for C26H25N3O4S2: C, 61.52; H, 4.96; N, 8.28; S, 12.63. Found: C, 59.30; H, 4.78; N, 7.95; S, 12.23.

Provenance & Evidence