Ammonium Hydroxide → HCID 178423697, compound

Participants

Reaction Conditions

Reaction Steps

In a 4 ml vial, the product of Example 91E (30 mg, 0.098 mmole), potassium fluoride (19 mg, 0.323 mmole) and tris(dibenzylideneacetone)dipalladium (5.3 mg, 0.0075 mmole) were charged and dried on high vacuum for 30 min. The product of Example 2A (34 mg, 0.147 mmole) was added followed by dioxane (1 ml) under nitrogen atmosphere. Tri-t-butylphosphine (10 wt % in hexane, 45 ul, 0.0147 mmole) was added last and the vial was sealed and heated at 85° C. overnight then 95° C. for 7 h. TLC (TLC conditions: 1% ammonium hydroxide and 10% methanol in dichloromethane on silica gel) showed a new spot besides the starting material. The reaction mixture was quenched with water and extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (eluted by 0.35% ammonium hydroxide and 3.5% methanol in dichloromethane) to give 6 mg (16% yield) of title compound. 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 7.93 (d, J=1.36 Hz, 1H), 7.89 (d, J=8.14 Hz, 1H), 7.47 (d, J=7.80 Hz, 1H), 7.30 (dd, J=8.48, 1.70 Hz, 1H), 7.08 (d, J=7.80 Hz, 1H), 3.80-3.94 (m, 1H), 3.46-3.60 (m, 1H), 3.02-3.15 (m, 1H), 2.66-2.84 (m, 3H), 2.60-2.61 (s, 3H), 2.50-2.54 (s, 3H), 2.26-2.40 (m, 2H), 1.62-2.04 (m, 4H), 1.43-1.58 (m, 1H), 1.15 (d, J=5.76 Hz, 3H). (M+H)+=378.

Provenance & Evidence