Sodium Hydroxide → 2-(6-Bromobenzo[d]thiazol-2-yl)-N-(2-sulfamoylethyl)acetamide

Participants

Reaction Steps

Ethyl 2-(6-bromobenzo[d]thiazol-2-yl)acetate (described in WO2011/074560, 250 mg, 0.83 mmol) in THF (4 mL) was treated with sodium hydroxide (1N NaOH, 0.92 mL, 0.92 mmol). After 2 hours, the reaction mixture was concentrated to dryness under reduced pressure, and the residue was co-evaporated with toluene (5 mL), re-dissolved in DMF (4 mL), and treated with 2-aminoethanesulfonamide hydrochloride (201 mg, 1.30 mmol), TEA (1.2 mL, 8.3 mmol) and HATU (475 mg, 1.30 mmol). After 16 hours, the reaction mixture was diluted with water (20 mL), extracted with DCM (3×10 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was dissolved in DMF/methanol and purified using reverse phase HPLC (Phenomemenx Luna AXIA 5 micron C18, 21.2×100 mm, 30 to 100% B over 15 minutes with 10 minute hold time, solvent A: 90% water/ACN/0.1% TFA, solvent B:90% ACN/water/0.1% TFA, Flow rate 20 mL/min; detector at 254). The pooled fractions were lyophilized to Compound A1a, (170 mg, 45% yield) as a white solid. HPLC: RT=0.75 (LCMS Method O). MS (ES): m/z=379.7 [M+H]+. 1H NMR (400 MHz, DMF-d7) δ 8.40 (d, J=2.0 Hz, 1H), 7.92 (d, J=8.8 Hz, 1H), 7.69 (dd, J=8.8, 2.0 Hz, 1H), 6.97 (s, 2H), 3.82-3.61 (m, 2H), 3.46 (s, 3H), 3.33 (dd, J=7.9, 6.4 Hz, 3H).

Provenance & Evidence