Water → 3-[2-[3-Amino-6-(4-tetrahydropyran-4-ylsulfonylphenyl)pyrazin-2-yl]ethynyl]phenol

Participants

Reaction Conditions

Reaction Steps

3-[2-(3-Amino-6-bromo-pyrazin-2-yl)ethynyl]phenol (50 mg, 0.1723 mmol), 4,4,5,5-tetramethyl-2-(4-tetrahydropyran-4-ylsulfonylphenyl)-1,3,2-dioxaborolane (85.70 mg, 0.2068 mmol) and K3PO4 (73.15 mg, 0.3446 mmol) were combined in MeCN (2 mL)/water (0.5 mL) and Pd[P(tBu)3]2 (4.403 mg, 0.008615 mmol) was added. The reaction was heated at 60° C. for 15 hours. The reaction was cooled to ambient temperature and diluted with EtOAc and 1M HCl. The layers were separated and the aqueous layer extracted with EtOAc (×3). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion™, 12 g column, eluting with 0 to 100% EtOAc/Petroleum Ether, dry loaded) followed by purification by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the title compound as a yellow solid (14 mg, 17% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.30-1.41 (m, 2H), 1.56 (d, 2H), 3.07-3.12 (m, 2H), 3.34-3.40 (m, 2H), 3.71 (dd, J=3.9, 11.4 Hz, 1H), 6.67-6.70 (m, 1H), 6.94 (br s, 2H), 6.95 (d, 1H), 7.01 (d, 1H), 7.07 (t, 1H), 7.70 (d, 2H), 8.05 (d, 2H), 8.55 (s, 1H) and 9.57 (s, 1H) ppm; MS (ES+) 436.1.

Provenance & Evidence