Hydrochloric Acid → HCID 178505096, compound

In a 5-mL round bottom flask, a solution of Example 176 (25 mg, 0.049 mmol), 1,1′-thiocarbonyldiimidazole (13.75 mg, 0.073 mmol), and 1,8-diazabicyclo[5.4.0]undec-7-ene (30.1 μL, 0.195 mmol) in anhydrous acetonitrile (490 μL) was stirred under nitrogen at 25° C. for 2 hours. The reaction was diluted with ethyl acetate (50 mL) and H2O (10 mL), and the pH was adjusted to ˜3 with 1 N aqueous HCl. The layers were separated, and the organic phase was washed with brine (10 mL), dried over anhydrous MgSO4, filtered, and concentrated by rotary evaporation. The crude material was purified by SiO2 flash chromatography (Alltech Extract-Clean™ column, 10 g bed) eluting with a step gradient of 5% to 7.5% methanol/CH2Cl2 to afford the title compound as a yellow solid (22 mg, 0.039 mmol, 80%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.50-0.62 (m, 1H), 0.81-0.91 (m, 1H), 0.94-1.04 (m, 2H), 1.73-1.89 (m, 2H), 2.34-2.42 (m, 1H), 2.56-2.66 (m, 2H), 3.17 (s, 3H), 3.66-3.85 (m, 2H), 7.10 (s, 1H), 7.35 (t, J=8.89 Hz, 2H), 7.40 (s, 2H), 7.90 (s, 1H), 7.95 (dd, J=8.08, 5.80 Hz, 2H); MS (ESI+) m/z 554 (M+H)+, 1107 (2M+H)+; MS (ESI−) m/z 552 (M−H)−, 1105 (2M−H)−.

1. customThe layers were separated
2. washthe organic phase was washed with brine (10 mL)
3. dry with materialdried over anhydrous MgSO4
4. filtrationfiltered
5. concentrationconcentrated by rotary evaporation
6. customThe crude material was purified by SiO2 flash chromatography (Alltech Extract-Clean™ column, 10 g bed)
7. washeluting with a step gradient of 5% to 7.5% methanol/CH2Cl2

ORD record

ord-8b88126991364076a1a785eafc40b8fb

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09173887B2