Sodium Bicarbonate → 5-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(3-oxetanyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Participants

Reaction Conditions

Reaction Steps

To 5-bromo-7-(3-oxetanyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (50 mg, 0.186 mmol) and 1-[(2,5-difluorophenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole (104 mg, 0.260 mmol) were added 1,4-Dioxane (2 mL) and sat. NaHCO3 solution (1 mL) in a 5 ml sealable vial. N2 gas was bubbled through the mixture for 10 minutes then Pd(Ph3P)4 (21.47 mg, 0.019 mmol) was added and bubbled N2 for 5 minutes. The mixture was then capped and heated 100° C. overnight. The reaction was diluted with water (3 ml) then extracted with EtOAc (4×5 ml). The organics were then combined, washed with brine, dried over MgSO4, filtered and concentrated. The residual was then diluted with 3 ml of DMSO and purified on 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, 15% ACN/H2O, 0.1% TFA to 40% 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 organic was combined wash with saturated NaCl solution, dried over MgSO4, filtered and concentrated. The material was then transferred into a 40 mL vial with MeCN then water was added and the solution was freeze-dried to give 5-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(3-oxetanyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (53 mg, 61.8% yield) as a white power. LC-MS (ES) m/z=462.4 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.15 (d, J=3.28 Hz, 1H), 8.08-8.13 (m, 1H), 7.70 (d, J=3.03 Hz, 1H), 7.41 (br. s., 1H), 7.15-7.33 (m, 4H), 6.17 (br. s., 2H), 5.82-5.93 (m, 1H), 4.95-5.07 (m, 4H), 4.30 (br. s., 2H), 3.96 (br. s., 2H), 3.29 (d, J=1.01 Hz, 2H).

Provenance & Evidence