HCID 71062175, compound → HCID 71062428, compound

Participants

Reaction Steps

To N,N-dibutyl-4-chloro-5-(2-hydroxyethyl)-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (Example 170, 27 mg, 0.035 mmol) in acetone (640 μL) was added Jones reagent (39 μL, 0.11 mmol). The resulting reaction mixture was stirred at room temperature for 25 min. Additional Jones reagent (39 μL, 0.11 mmol) was added and stirring was continued for 1.5 h. The reaction mixture was then quenched with i-PrOH followed by water. The aqueous layer was extracted with EtOAc (3×), and the combined organics were washed with sat. aq. NaCl solution and dried over Na2SO4. After filtering through a pipette containing a small plug of CELITE®, concentration in vacuo afforded a yellow oil. The crude oil was purified by preparative HPLC to give the title compound (6 mg, 22%) as a white solid after lyophilization. 1H NMR (CD3OD, 2:1 mixture of amide rotamers) δ 8.56 (s, 1H), 8.19 (ddd, J=8.4 Hz, 3.2, 1.9 1H), 8.12 (d, J=1.8 Hz, 1H), 8.04-7.99 (m, 2H), 7.96-7.90 (m, 2H), 7.85 (dd, J=12.8, 8.4 Hz, 1H), 7.63-7.54 (m, 2H), 7.25-7.06 (m, 3.5H), 6.94 (d, J=7.0 Hz, 0.5H), 4.77-4.41 (m, 1.5H), 4.09 (br s, 0.5H), 3.79-3.38 (m, 5H), 3.24-2.67 (m, 5H), 1.60-0.84 (m, 11H), 0.78 (t, J=7.3 Hz, 2H), 0.71-0.65 (m, 1H); MS(ESI+) m/z 784.3 (M+H)+.

Provenance & Evidence