Sulfuric acid magnesium salt (1:1) → HCID 53251118, compound

Temperature

100 °C

Bis(tri-t-butylphosphino)palladium (18.9 mg, 0.057 mmol; Aldrich), 3-ethynylpyridine (117 mg, 1.131 mmol; Aldrich), MgSO4 (68 mg, 0.57 mmol), sodium t-butoxide (136 mg, 1.41 mmol; Aldrich) and the product of Example 1A (150 mg, 0.57 mmol) were suspended in dioxane (5 mL). The mixture was purged with a nitrogen stream for 2 minutes, then stirred under nitrogen at 100° C. for 2 hours in a sealed tube. The mixture was cooled to room temperature, filtered though a glass microfiber frit, rinsed with CH3OH (3 mL) and purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 40-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound: 1H NMR (400 MHz, methanol-d4) δ ppm 2.54 (s, 3H), 2.88 (t, J=6.0 Hz, 2H), 2.98 (t, J=5.6 Hz, 2H), 3.68 (s, 2H), 7.01 (t, J=7.6 Hz, 1H), 7.27 (dd, J=7.3, 0.9 Hz, 1H), 7.43 (dd, J=7.9, 0.9 Hz, 1H), 7.46 (ddd, J=7.9, 5.0, 0.8 Hz, 1H), 8.06 (dt, J=7.9, 1.8 Hz, 1H), 8.49 (dd, J=5.0, 1.7 Hz, 1H), 8.81 (dd, J=2.1, 0.9 Hz, 1H); MS (APCI) m/z 288 (M+H)+.

1. customThe mixture was purged with a nitrogen stream for 2 minutes
2. temperatureThe mixture was cooled to room temperature
3. filtrationfiltered though a glass microfiber frit
4. washrinsed with CH3OH (3 mL)
5. custompurified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 40-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

ORD record

ord-ca32d907e4d44083b3a014701243d785

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08809532B2