Lithium Hexamethyldisilazide → HCID 67347606, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred mixture of 4-(7-(6-chloropyridin-3-yloxy)thieno[3,2-b]pyridin-2-yl)-N-methylbenzamide (Example 130, Step B, 78 mg, 0.197 mmol), lithium bis(trimethylsilyl)amide (LHMDS, 0.433 mL, 0.433 mmol, 1M in hexanes), and Pd2(dba3) (9.02 mg, 0.00985 mmol), was added P,P-dicyclohexyl(3-(2-N, N-dimethylaminophenyl)-phenyl)phosphine (7.75 mg, 0.0197 mmol). The mixture was sparged with nitrogen for 2 minutes, and then heated to 80° C. for 18 hours. After cooling to room temperature, 2N aqueous HCl (0.5 mL) was added and stirring was continued for 1 hour at room temperature. The mixture was partitioned between dichloromethane (5 mL) and 1:1 saturated aqueous NaHCO3/water (5 mL). The phases were separated, and the aqueous phase was re-extracted with dichloromethane (2×2 mL). The combined organic phases were dried (Na2SO4), filtered, and concentrated. The crude was purified by preparative TLC plate (1 mm thickness, Rf=0.45) eluting with 15% MeOH/CHCl3. The product was obtained as a beige, waxy solid (11 mg, 12%). 1H NMR (400 MHz, 1:1 CDCl3/CD3OD) δ 8.44 (d, J=5 Hz, 1H), 7.84-7.95 (m, 6H), 7.41 (m, 1H), 6.71 (d, J=9 Hz, 1H), 6.63 (d, J=5 Hz, 1H), 2.97 (s, 3H).

Provenance & Evidence