Lithium Hydroxide → HCID 58318865, compound

Participants

Reaction Steps

Compound 20 (300 mg, 1.15 mmol, 1.00 eq) was dissolved in Dioxane (5.0 mL), and 1N LiOH (5.0 mL) was added. The reaction was stirred at rt for 45 minutes. The reaction was quenched with 1N HCl (5.0 mL) and extracted (3×) with ether. The combined organics were dried (MgSO4), filtered, and concentrated in vacuo to afford 200 mg (70%) of crude 4-fluoro-3-(methyl(pyrimidin-5-yl)amino)benzoic acid as a yellow solid. The product was confirmed by LCMS (>90% @ 220 nm and 254 nm) and carried forward without purification. 4-fluoro-3-(methyl(pyrimidin-5-yl)amino)benzoic acid (30 mg, 0.12 mmol, 1.0 eq), 6-methylpyridin-2-amine (15 mg, 0.14 mmol, 1.2 eq), O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (91 mg, 0.24 mmol, 2.0 eq), and N,N-Diisopropylethylamine (85 mg, 0.66 mmol, 5.5 eq) were dissolved in DMF (0.98 mL) and stirred at rt overnight. The reaction was quenched with water, and the layers were separated via phase separation. The organic layer was dried on air concentrator and purified by mass directed preparatory HPLC to afford 15 mg (36%) of the title compound as a mono-TFA salt: 1H NMR (400 MHz, DMSO-d6) δ 10.91 (s, 1H), 8.65 (s, 1H), 8.28 (s, 2H), 8.14 (dd, J=7.7, 2.2 Hz, 1H), 8.00-7.94 (m, 2H), 7.75 (t, J=7.9 Hz, 1H), 7.48 (dd, J=10.7, 8.7 Hz, 1H), 7.05 (dd, J=7.4, 1H), 3.39 (s, 3H), 2.45 (s, 3H); ES-MS [M+1]+:338.1.

Provenance & Evidence