Dimethyl Sulfoxide → 5-((1R)-1-{[(tert-butylamino)carbonyl]amino}ethyl)-N-hydroxythiophene-2-carboxamide

Participants

Reaction Steps

To the vial containing (R)-4-(1-aminoethyl)benzoic acid hydrochloride from Step 1 was added tert-butyl isocyanate (0.026 mL, 0.23 mmol), N,N dimethylformamide (2.5 mL) and triethylamine (0.21 mL, 1.50 mmol). After the reaction was stirred at rt for 16 h, HATU (0.057 g, 0.150 mmol) in N,N-dimethylformamide (0.5 mL) was added, immediately followed by the addition of O-(tert-butyldimethylsilyl)hydroxylamine (0.0331 g, 0.225 mmol) in DCM (1.0 mL). This mixture was shaken at rt for 1 hr after which it was evaporated to dryness. To the resulting residue was added hydrochloric acid (4 mL, 1% in IPA). After shaking at rt for 30 min, solid NaHCO3 was added to quench excess acid and the solvent was then completely evaporated to dryness to give a solid residue. This solid was dissolved in DMSO (1.2 mL), and the solution was filtered and purified via Gilson prep-HPLC to give the title compound (0.015 g, 35%) as a white solid. LC-MS: (FA) ES+ 286; 1H NMR (Methanol-d4, 300 MHz) δ 7.41 (m, 1H), 6.91 (d, J=4.7 Hz, 1H), 5.03 (q, J=6.8 Hz, 1H), 2.03 (m, 4H), 1.96 (m, 8H), 1.69 (m, 8H), 1.47 (d, J=7.0 Hz, 3H).

Provenance & Evidence