Dichloromethane → ethyl ((1S)-5-{3-[[2-(4-ethylphenyl)-5-methyl-4-pyrimidinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

Participants

Reaction Conditions

Reaction Steps

To a mixture of toluene (12 mL) and 1,4-dioxane (2.5 mL) were added ethyl ((1S)-5-{3-[(2-chloro-5-methyl-4-pyrimidinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (Example 342, 205 mg, 0.49 mmol), 4-ethylphenyl boronic acid (294 mg, 1.96 mmol), and PdCl2(dppf).CH2Cl2 (35.9 mg, 0.05 mmol). A flow of argon was passed through the reaction mixture for 30 min, then Na2CO3 (2.45 mL, 4.91 mmol, 2 M aqueous solution) was added, and the reaction was stirred at 75° C. for 18 h. After cooling to rt, the reaction mixture was diluted with EtOAc, and washed with a saturated aqueous solution of NaHCO3. The organic layer was then dried (Na2SO4), filtered, and then concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (4:1 hexanes/EtOAc) to provide the product (140 mg, 59%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 1.26-1.32 (m, 6H), 1.73-1.80 (m, 1H), 2.16-2.19 (m, 2H), 2.33 (s, 3H), 2.35-2.42 (m, 2H), 2.67-2.88 (m, 5H), 3.22 (s, 3H), 3.51-3.55 (m, 1H), 3.79 (t, 2H), 4.00 (t, 2H), 4.19 (q, 2H), 6.69 (d, 1H), 6.75 (s, 1H), 7.04 (d, 1H), 7.26 (d, 2H), 8.08 (s, 1H), 8.30 (d, 2H).

Provenance & Evidence