N-(6-(2-Chloropyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide → HCID 25182146, compound

Participants

Reaction Steps

N-(6-(2-Chloropyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide (59.0 mg, 194 μmol) was suspended in THF (1.8 mL) to which tetrakis(triphenylphosphine)palladium (25.6 mg, 22 μmol) and benzylzinc bromide, 0.5 m solution in THF (0.55 mL, 275 μmol) were added under argon, and the reaction solution was stirred at RT. After about 2 hours, the reaction was heated to 80° C., and stirring was continued under argon. After about 100 minutes, additional Pd(PPh3)4 (21 mg) and benzylzinc bromide (0.57 mL) were added, and the reaction was stirred. After another hour or so, additional benzylzinc bromide (0.73 mL) was added, and stirring was continued at 80° C. The reaction was stirred overnight and quenched with saturated ammonium chloride (1.5 mL) and 0.5 M EDTA (2.5 mL), extracted with 10:1 DCM/MeOH, and the organic phases were dried over sodium sulfate, filtered through Celite®(diatomaceous earth), and concentrated. The crude concentrate was purified on a silica gel column (20:1 to >5:1 DCM/MeOH), and the product-containing fractions were collected, concentrated, and washed with Et2O and MeOH and filtered. The solid was collected and purified on HPLC (10% to >95% MeCN/water with 0.1% TFA over 40 minutes), to provide N-(6-(2-benzylpyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide (8 mg, 11% yield). MS (ESI pos. ion) m/z: 361. Calculated exact mass for C20H16N4OS: 360. 1H NMR (400 MHz, DMSO-d6): 12.50 (s, 1H), 8.85 (s, 1H), 8.78 (d, J=5.5 Hz, 1H), 8.29 (d, J=8.0 Hz, 1H), 7.95 (d, J=5.5 Hz, 1H), 7.85 (d, J=8.5 Hz, 1H), 7.38 (m, 2H), 7.31 (m, 2H), 7.21 (m, 1H), 4.28 (s, 2H), 2.23 (s, 3H).

Provenance & Evidence