1,4-Dioxane → 7-[2-(4-morpholinyl)ethyl]-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Participants

Reaction Conditions

Reaction Steps

To 5-bromo-7-[2-(4-morpholinyl)ethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (50 mg, 0.153 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indole (93 mg, 0.215 mmol) were added 1,4-Dioxane (2 mL) and sat. NaHCO3 (1 mL) in a 5 ml sealable vessel. The mixture was then bubbled with N2 gas for 5 minutes then added Pd(Ph3P)4 (17.71 mg, 0.015 mmol) and the reaction was capped and heated at 100° C. overnight. The reaction was then diluted with water (2 ml) then extracted with EtOAc (3×3 ml). The organics were then combined and washed with brine, dried over MgSO4, filtered, and concentrated. The residue was dissolved in 3 mL of DMSO and then purified by HPLC: (HPLC condition: Gilson using Trilution software with a Sunfire 5u C18(2) 100A. 50×30.00 mm 5 micron. 7.3-minute run (47 ml/min, 18% ACN/H2O, 0.1% TFA to 43% ACN/H2O, 0.1% TFA) with UV detection at 220 nm). Product fractions were combined and the volume was reduced to remove most of the MeCN. To the water left behind was added saturated NaHCO3 and then the mixture was extracted with EtOAc (3×15 mL). The organics were combined, washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated. Then the product was transferred into a 40 mL vial with MeCN then added water and freeze-dried to give 7-[2-(4-morpholinyl)ethyl]-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (35 mg, 41.5% yield) as a white solid. LC-MS (ES) m/z=551.5 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.10-8.15 (m, 2H), 7.69 (s, 1H), 7.56-7.66 (m, 3H), 7.33 (s, 2H), 7.24 (d, J=8.34 Hz, 1H), 6.06 (br. s., 2H), 4.24-4.31 (m, 4H), 4.04 (s, 2H), 3.54 (br. s., 4H), 3.22-3.29 (m, J=7.83 Hz, 2H), 2.71 (br. s., 2H), 2.46 (br. s., 4H).

Provenance & Evidence