1,4-Dioxane → 7-(3-methylbutyl)-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-(3-methylbutyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (75 mg, 0.265 mmol) and 5-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indole (160 mg, 0.371 mmol) were added 1,4-Dioxane (2 mL) and saturated NaHCO3 (1 mL) in a 5 ml sealable vessel. The mixture was then bubbled with N2 gas for 5 minutes then Pd(Ph3P)4 (30.6 mg, 0.026 mmol) was added and the vessel was capped. The reaction was then 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 crude was dissolved in 3 mL of DMSO and the product 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, 40% ACN/H2O, 0.1% TFA to 65% ACN/H2O, 0.1% TFA) with UV detection at 254 nm). Product fractions were combined and the volume was reduced to remove most of the MeCN. The water left behind was added saturated NaHCO3 and then extracted with EtOAc (3×15 mL). The organics were combined and washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated. The material was transferred to a 40 mL vial with MeCN then water was added and the solution was freeze-dried. to afford 7-(3-methylbutyl)-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (67 mg, 0.132 mmol, 49.8% yield) as a white solid. LC-MS (ES) m/z=508.5 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.15 (s, 1H), 8.11 (d, J=8.34 Hz, 1H), 7.69 (s, 1H), 7.56-7.66 (m, 3H), 7.33 (s, 2H), 7.24 (d, J=8.34 Hz, 1H), 6.10 (br. s., 2H), 4.27 (t, J=8.46 Hz, 2H), 4.18 (t, J=7.33 Hz, 2H), 4.03 (s, 2H), 3.26 (t, J=8.34 Hz, 2H), 1.69 (q, J=6.99 Hz, 2H), 1.50 (dt, J=6.69, 13.39 Hz, 1H), 0.93 (d, J=6.57 Hz, 6H).

Provenance & Evidence