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

Participants

Reaction Conditions

Reaction Steps

To mixture of 4-methoxyphenylboronic acid (28.5 mg, 0.183 mmol) and ethyl ((1S)-5-{3-[(2,5-dichloro-4-pyrimidinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (Example 442, 80 mg, 0.183 mmol) in toluene (6.72 mL) and 1,4-dioxane (1.68 mL) was added PdCl2(dppf).CH2Cl2 (15 mg, 0.018 mmol). The mixture was purged with argon for 15 min after which a 2 M Na2CO3 aqueous solution (1.68 mL, 1.83 mmol) was added. The mixture was stirred and heated at 75° C. for 2 h, the reaction mixture was allowed cool to rt, and then washed with a saturated aqueous solution of NaHCO3. The organic layer was separated and the aqueous phase extracted with EtOAc (2×). The combined organic phases were dried, filtered, and then concentrated under reduced pressure. The residue was purified by silica gel flash column chromatography (1:3 EtOAc/Hexanes) to give the product (74 mg, 79%). 1H NMR (400 MHz, CDCl3): δ 1.25 (t, 3H), 1.70-1.79 (m, 1H), 2.15-2.20 (m, 2H), 2.28-2.42 (m, 2H), 2.66 (dd, 1H), 2.72-2.90 (m, 2H), 3.31 (s, 3H), 3.44-3.54 (m, 1H), 3.82 (s, 3H), 3.84 (t, 2H), 3.95 (t, 2H), 4.16 (q, 2H), 6.65 (d, 1H), 6.72 (s, 1H), 6.91 (d, 2H), 7.05 (s, 1H), 8.15 (s, 1H), 8.25 (d, 2H); LC-MS: RT=3.51 min, (M+H)+ 510.5.

Provenance & Evidence