7-[2-(4-Morpholinyl)ethoxy]-2-(4-nitrophenyl)imidazo[2,1-b]benzothiazole synthesis

Yield:950769-60-5 96%

Reaction Conditions:

with tetra-(n-butyl)ammonium iodide;potassium carbonate in N,N-dimethyl-formamide at 90 - 95; for 5 h;

Steps:

4.C

1. A 50 L 3 -neck round bottom flask was equipped with a mechanical agitator, thermocouple probe, drying tube, reflux condenser, and a heating mantle.2. The flask was charged with 2-(4-nitrophenyl) imidazo [2,1- 6]benzothiazol-7-ol (1.770 Kg), N,N-dimethylformamide (18.0 L), 4-(2- chloroethyl)morpholine hydrochloride (2.751 Kg), potassium carbonate (2.360 Kg) and tetrabutylammonium iodide (0.130 Kg) with stirring.3. The resulting yellow suspension was heated to 90⁰C to 95 ⁰C, maintaining the temperature for approximately 5 hours.4. The reaction was monitored by TLC until no starting material was observed. (20% methanol/ethyl acetate; R_f (product) = 0.15; R_f (starting material) = 0.85).5. The reaction mixture was cooled to ~10°C, the yellow solids collected by filtration onto a polypropylene filter pad. The solids were slurried in water (2 x 5 L) and filtered.6. The crude wet product was slurried in acetone (5 L), filtered and the solids rinsed with acetone (2 x 1.5 L).7. The solids were dried in a vacuum oven (<10mmHg) at 45°C. Yield: 2.300 Kg (95%), yellow solid.TLC: R/= 0.15 (20% methanol/EtOAc)HPLC: 95.7% (area)¹H NMR: conforms (300 MHz, DMSO) Table 5.

References:

WO2010/54058,2010,A1 Location in patent:Page/Page column 76-78