2-Aminothiazole → HCID 71586127, compound

Participants

Reaction Conditions

Reaction Steps

A round bottom flask was charged with 2-aminothiazole (20.26 mg, 0.202 mmol) and sealed with septum. THF (1686 μl) was added and the solution was cooled to 0° C. A THF solution of lithium bis(trimethylsilyl)amide (253 μl, 0.253 mmol, 1 M) was added and the solution was maintained at 0° C. for 5 min To this solution was added 5-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)naphthalene-2-sulfonyl chloride (76.0 mg, 0.169 mmol) as a solution in THF (3 mL total). After 15 minutes at 0° C., saturated aqueous NH4Cl (1 mL) was added to the reaction mixture. The reaction mixture was partitioned between saturated aqueous NH4Cl (10 mL) and EtOAc (15 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×10 mL). The combined organic extracts were dried over Na2SO4 and concentrated under a vacuum. The residue was taken up in minimal DMSO and purified by preparative HPLC (column: Phenomenex C18 150×30 mm, 5 μm (Phenomenex, Torrance, Calif.): 20 to 90% CH3CN:H2O (1% TFA modifier) over 15 min). Fractions were combined and concentrated to afford 5-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)naphthalene-2-sulfonamide (50.0 mg, 0.097 mmol) as a white amorphous solid. 1H NMR (400 MHz, d6-acetone) δ ppm 3.50 (s, 3H) 5.84 (d, J=1.86 Hz, 1H) 6.74 (d, J=4.69 Hz, 1H) 7.02 (d, J=1.96 Hz, 1H) 7.19 (d, J=4.70 Hz, 1H) 7.46 (d, J=7.04 Hz, 1H) 7.51-7.59 (m, 1H) 7.64 (d, J=8.90 Hz, 1H) 7.72 (d, J=8.02 Hz, 1H) 7.75-7.82 (m, 1H) 7.87 (s, 1H) 7.94 (d, J=8.12 Hz, 1H) 8.05 (d, J=8.31 Hz, 1H) 8.44 (s, 1H); m/z (ESI, +ve ion) 515.2 (M+H)+.

Provenance & Evidence