Nitrogen → 1,1-dimethylethyl 3-(4-amino-5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-azetidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

To 1,1-dimethylethyl 3-(4-amino-5-bromo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-azetidinecarboxylate (200 mg, 0.543 mmol), and 1-[(3-methylphenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole (246 mg, 0.652 mmol) dissolved in 1,4-Dioxane (4 mL) was added Sat NaHCO3 (2 mL). The mixture was then bubbled N2 gas for 10 minutes then added Pd(Ph3P)4 (62.8 mg, 0.054 mmol) then bubbled for 5 additional minutes. Then reaction was then capped and heated at 100° C. overnight. The mixture was let cool then diluted with water (10 mL) then extracted with EtOAc (3×20 ml). The organics were combined, washed with brine, dried over MgSo4, filtered and concentrated to give an amber color oil. The oil was then purified on a 25 g Biotage SNAP column conditioned with Hexane using a gradient of 0 to 10% MeOH in DCM for 30 minutes to isolate 1,1-dimethylethyl 3-(4-amino-5-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-azetidinecarboxylate (197 mg, 0.366 mmol, 67.3% yield) as a amber color solid. LC-MS (ES) m/z=539.3 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.11-8.18 (m, 2H), 7.60 (s, 1H), 7.37 (s, 1H), 7.28 (d, J=8.34 Hz, 1H), 7.20-7.26 (m, 1H), 7.06-7.15 (m, 3H), 5.76 (s, 1H), 5.46-5.56 (m, 1H), 4.33 (d, J=8.08 Hz, 4H), 4.21 (t, J=8.46 Hz, 2H), 3.93 (s, 1H), 3.83 (s, 2H), 3.22 (t, J=8.21 Hz, 2H), 2.31 (s, 3H), 1.43 (s, 9H).

Provenance & Evidence