Potassium Carbonate → HCID 44124933, compound

Participants

Reaction Conditions

Reaction Steps

A vial containing (R)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazole (Example 64A, 23 mg, 0.056 mmol), methyl 6-bromo-2-pyridinecarboxylate (12 mg, 0.056 mmol), bis(triphenylphosphine)palladium(II) chloride (5 mg, 7 μmol), and K2CO3 (23 mg, 0.17 mmol) in methanol (0.5 mL) was heated to 80° C. for 2 hours and cooled. The mixture was filtered and concentrated. The residue was purified by preparative HPLC on a Phenomenex Luna C8(2) 5 um 100 Å AXIA column (30 mm×75 mm). A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 50 mL/minute (0-0.5 minutes 10% A, 0.5-7.0 minutes linear gradient 10-95% A, 7.0-10.0 minutes 95% A, 10.0-12.0 minutes linear gradient 95-10% A). Samples were injected in 1.5 mL dimethyl sulfoxide:methanol (1:1). A custom purification system was used, consisting of the following modules: Waters LC4000 preparative pump; Waters 996 diode-array detector; Waters 717+ autosampler; Waters SAT/IN module, Alltech Varex III evaporative light-scattering detector; Gilson 506C interface box; and two Gilson FC204 fraction collectors. The system was controlled using Waters Millennium32 software. Fractions were collected based upon UV signal threshold and selected fractions subsequently analyzed by flow injection analysis mass spectrometry using positive APCI ionization on a Finnigan LCQ using 70:30 methanol: 10 mM NH4OH(aqueous) at a flow rate of 0.8 mL/minute. Loop-injection mass spectra were acquired using a Finnigan LCQ running LCQ Navigator 1.2 software and a Gilson 215 liquid handler for fraction injection. The title compound was obtained as the bis trifluoroacetate salt. 1H NMR (300 MHz, CD3OD) δ ppm 1.52-1.68 (m, 1H), 1.74-1.93 (m, 3H), 1.95-2.09 (m, 2H), 2.32-2.47 (m, 1H), 2.64-2.75 (m, 1H), 3.02-3.23 (m, 2H), 3.51-3.76 (m, 3H), 3.79-3.95 (m, 2H), 4.08-4.22 (m, 2H), 7.64 (d, J=8.5 Hz, 1H), 7.99-8.09 (m, 2H), 8.10-8.17 (m, 2H), 8.62 (d, J=1.7 Hz, 1H); MS (DCI/NH3) m/z 409 (M+H)+.

Provenance & Evidence