N-benzyl-2-chloroacetamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloromethylthiazole (1.33 g, 10.0 mmol) and benzylamine (2.2 mL, 20.0 mmol) were mixed together and heated to 80° C. for 24 hours and allowed to cool to room temperature. The solid mass was treated with 2M aqueous sodium carbonate and stirred until the mass was broken up and the mixture was extracted with 2 portions of ethyl ether. The combined organic extracts were dried (Na2SO4), filtered, and concentrated. The residue was dissolved in 40 mL of dichloromethane, cooled to 0° C., and 40 mL of saturated, aqueous NaHCO3 was added. To this stirred biphasic mixture was added chloroacetyl chloride (1.8 mL, 22.0 mmol) dropwise and mixture was stirred for an additional 2 hours at 0° C. The layers were separated and the organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (silica gel, 30% -50% ethyl acetate/hexanes) to provide first, 0.58 g (21%) N-benzylchloroacetamide followed by 0.76 g (27%) of the title compound. to cool to room temperature the mixture was extracted with 2 portions of ethyl ether The combined organic extracts were dried (Na2SO4) filtered concentrated The residue was dissolved in 40 mL of dichloromethane cooled to 0° C. 40 mL of saturated, aqueous NaHCO3 was added mixture was stirred for an additional 2 hours at 0° C The layers were separated the organic phase was dried (Na2SO4) filtered concentrated The residue was purified by column chromatography (silica gel, 30% -50% ethyl acetate/hexanes) to provide first

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-pyridin-2-ylpiperazine (24 mg, 0.15 mmol, Aldrich), N-benzyl-2-chloroacetamide (37 mg, 0.20 mmol, Maybridge) and sodium carbonate (50 mg) in N,N-dimethylformamide/water (2:1, 2 mL) was shaken at room temperature for 18 hours. The resulting mixture was decanted, concentrated under reduced pressure and the residue purified by preparative HPLC to provide 16 mg (32%) of the desired product. 1H NMR (500 MHz, DMSO-d6) δ 2.58 (m, 4H), 3.05 (s, 2H), 3.52 (m, 4H), 4.35 (d, J=5 Hz, 2H), 6.63 (t, J=5 Hz, 1H), 6.82 (d, J=6 Hz, 1H), 7.28 (m, 5H), 7.55 (t, J=6 Hz, 1H), 8.12 (t, J=5 Hz, 1H), 8.35 (s, 1H); MS (ESI/APCI+) m/e 311 (M+H)+. The resulting mixture was decanted concentrated under reduced pressure the residue purified by preparative HPLC

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir: