Ethylenediamine → HCID 86666556, compound

Participants

Reaction Steps

To a mixture of resin of triphenylphosphine (54.6 mg, 0.114 mmol) in THF (0.6 mL) was added 3,5-difluorophenol (10.1 mg, 0.0778 mmol) and di-tert-butyl azodicarboxylate (19.1 mg, 0.0830 mmol). The mixture was stirred for 15 minutes before adding 4-(4-hydroxypiperidin-1-yl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile (25.0 mg, 0.0519 mmol). The reaction was stirred overnight at room temperature and the solvent was evaporated. The vial and resin were washed with DCM and filtered. The filtrates were washed with 10% aq. NaOH solution. The organic was collected and concentrated to give the crude product. The crude residue was dissolved in methylene chloride (0.20 mL) and trifluoroacetic acid (0.17 mL) was added. The mixture was stirred for 2 hours then concentrated. The residue was dissolved in methanol (0.5 mL) followed by adding ethylenediamine (0.10 mL, 1.50 mmol). After stirring for 1 hour, the mixture was diluted with acetonitrile and purified by preparative LCMS (C18 column eluting with a gradient of acetonitrile (ACN)/H2O containing 0.1% trifluoroacetic acid (TFA)) to afford the desired product (12.6 mg, 30%). 1H NMR (CD3OD) δ9.08 (s, 1H), 8.92 (s, 1H), 8.60 (s, 1H), 7.86 (s, 1H), 7.27 (s, 1H), 6.64 (d, 2H), 6.54 (t, 1H), 5.56 (m, 1H), 4.70 (s, 1H), 4.21 (t, 2H), 3.74 (d, 1H), 3.52 (br, 2H), 3.28 (m, 4H), 2.15 (m, 4H). LCMS (M+H)+: 464.1.

Provenance & Evidence