Hydrochloric Acid → HCID 71711177, compound

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with INTERMEDIATE D (0.100 g, 0.192 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (Sigma-Aldrich, St. Louis, Mo., 0.113 g, 0.384 mmol), tetrakis(triphenylphosphine)palladium(0) (0.022 g, 0.019 mmol), and K2CO3 (0.133 g, 0.959 mmol). The solids were diluted with dioxane (1.279 mL) and water (0.639 mL), and the reaction was heated under microwave irradiation at 100° C. for 30 minutes. The reaction mixture was lyophilized overnight and the material was then taken up in methanol, and acidified with HCl (1N) (3.84 mL, 3.84 mmol). The mixture was concentrated onto silica gel, and purified via silica gwel MPLC (Biotage Isolera One; PuriFlash HP, 15μ, 25 g), eluting with 0 to 100% ethyl acetate in heptane to yield slightly impure material. The material was loaded onto a 500 mg SCX column and the product was eluted (with impurity) in the ammonia wash. The resulting material was then purified by reverse-phase preparative HPLC (Column: Phenomenex 150×30 mm, 5 micron, C18 column; 0.1% TFA in CH3CN/H2O, gradient 25% to 90% over 20 min) to provide 4-(2-(1H-pyrazol-4-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.022 g, 0.043 mmol) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.47 (m, J=12.80 Hz, 2H) 4.28-4.37 (m, 2H) 6.25 (d, J=8.51 Hz, 1 H) 7.08 (dd, J=8.56, 2.20 Hz, 1 H) 7.14 (d, J=2.15 Hz, 1 H) 7.59-7.64 (m, 1 H) 7.65-7.70 (m, 1 H) 7.96 (s, 2 H) 8.02 (d, J=1.37 Hz, 1 H) 8.43 (s, 1 H). m/z (ESI) 509.0 (M+H)+.

Provenance & Evidence