Sodium Bicarbonate → HCID 66823851, compound

Participants

Reaction Conditions

Reaction Steps

To 5-bromo-7-(1-methylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (100 mg, 0.392 mmol) and 1-[(2,5-difluorophenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole (188 mg, 0.470 mmol) was added 1,4-Dioxane (2 mL) and saturated NaHCO3 (1 mL) in a 5 ml sealable vial. The mixture was then bubbled with N2 for 10 minutes then Pd(Ph3P)4 (45.3 mg, 0.039 mmol) was added and bubbled for an additional 5 minutes. It was then capped and heated at 100° C. overnight. The reaction was then checked with LCMS and 10% of the bromide starting material remained. 50 mg of the boronic ester was added, and the reaction was capped and heated at 100° C. for an additional 5 hr. The reaction was diluted with water (5 ml) then extracted with EtOAc (3×10 ml). The organics wer combined, washed with brine and dried over MgSO4, filtered and concentrated. The residual oil was then diluted with DMSO (3 mL) then 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, 28% ACN/H2O, 0.1% TFA to 53% 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. To the water left behind was added saturated NaHCO3 and then the mixture was extracted with EtOAc (3×15 mL). The organics were combined and washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated. The product was transferred into a 40 mL vial with MeCN then added water and freeze-dried to isolate 5-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(1-methylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (76 mgt, 43.3% yield) as a white solid. LC-MS (ES) m/z=448.4 [M+H]+1H NMR (400 MHz, DMSO-d6) δ 8.13 (s, 1H), 8.09 (d, J=8.08 Hz, 1H), 7.42 (s, 1H), 7.36 (s, 1H), 7.14-7.30 (m, 4H), 6.08 (br. s., 2H), 4.97 (quin, J=6.76 Hz, 1H), 4.29 (t, J=8.46 Hz, 2H), 3.95 (s, 2H), 3.27 (t, J=8.46 Hz, 2H), 1.46 (d, J=6.82 Hz, 6H).

Provenance & Evidence