Diisopropylethylamine → 2-Methyl-6-{[2-(1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yl]oxy}benzo[b]thiophene-3-carboxylic acid cyclopropylamide

Temperature

0 °C

To a solution of 2-methyl-6-{[2-(1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yl]oxy}benzo[b]thiophene-3-carboxylic acid 117b (75 mg, 0.18 mmole) in DMF (1.5 mL) at 0° C. were added N,N-diisopropylethylamine (68 μL, 0.39 mmole) and HBTU (100 mg, 0.27 mmole). The reaction mixture was stirred 30 min at 0° C. then warmed to room temperature and stirred 18 hr. The mixture was poured onto H2O (25 mL) and the precipitate was collected by vacuum filtration. The filter paper was extracted with a mixture of CH2Cl2 (10 mL) and MeOH (10 mL). The solution was concentrated and the crude mixture was purified by silica gel chromatography (5% MeOH/EtOAc) to afford a pale yellow solid (58 mg, 71%). 1H NMR (DMSO-d6, 300 MHz) δ8.52 (1H, d, J=5.46 Hz), 8.46 (1H, d, J=4.33 Hz), 7.95 (1H, d, J=2.26 Hz), 7.88 (1H, s), 7.80 (1H, d, J=8.67 Hz), 7.40 (1H, s), 7.32 (1H, dd, J=2.26, 8.85 Hz), 7.02 (1H, s), 6.70 (1H, d, J=5.46 Hz), 3.98 (3H, s), 2.90 (1H, m), 2.57 (3H, s); 0.73 (2H, m), 0.57 (2H, m).

1. temperaturethen warmed to room temperature
2. stirringstirred 18 hr
3. additionThe mixture was poured onto H2O (25 mL)
4. filtrationthe precipitate was collected by vacuum filtration
5. extractionThe filter paper was extracted with a mixture of CH2Cl2 (10 mL) and MeOH (10 mL)
6. concentrationThe solution was concentrated
7. customthe crude mixture was purified by silica gel chromatography (5% MeOH/EtOAc)

ORD record

ord-c2df7701505c4870ab09b6e367f795fc

Source dataset

uspto-grants-2005_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06869962B2