N-[(2,4-dichlorophenyl)methyl]piperidine-4-carboxamide

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

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

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

Procedure: To a 25 mL round-bottomed flask was added 2,4-dichloro-6-methyl-1,3,5-triazine (800 mg, 2.79 mmol) and N-[(2,4-dichlorophenyl)methyl]-4-piperidinecarboxamide (859 mg, 2.79 mmol) in acetonitrile (8.7 mL). Diisopropylethylamine (1.46 mL, 8.36 mmol) was added to give a yellow suspension. The reaction mixture was stirred at room temperature for 15 minutes, at which time LC-MS showed the reaction was complete. This suspension was filtered through a Buchner funnel to afford 1-(4-chloro-6-methyl-1,3,5-triazin-2-yl)-N-[(2,4-dichlorophenyl)methyl]-4-piperidinecarboxamide (596 mg, 1.44 mmol, 52%) as a white solid which was used in the next step without further purification. MS (ES) m/e 416 [M+H]+. to give a yellow suspension This suspension was filtered through a Buchner funnel

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

Procedure: A 500 mL round bottom flask equipped with a magnetic stir bar was charged with 1,1-dimethylethyl-4-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)-1-piperidinecarboxylate (27.6 g, 71.2 mmol) and DCM (117 mL) at room temperature. Trifluoroacetic acid (117 mL) was added slowly, and the reaction was maintained at room temperature for 1 hour after which time LC/MS determined that the reaction was complete (Rt=6.03 min and m/e 287 [M+1]+). The volatiles were removed by rotary evaporation and the crude oil was dissolved in ethyl acetate and washed with saturated sodium bicarbonate solution (3×200 mL). The organic phase was dried over Na2SO4, filtered and concentrated to give 13.5 g of N-[(2,4-dichlorophenyl)methyl]-4-piperidinecarboxamide (47 mmol, 66%) as a pale yellow solid. MS (ES) m/e 287 [M+H]+. 1H NMR (400 MHz, DMSO-D6) □ 8.6 (m, 1H), 7.4 (d, 1H), 7.3 (d, 1H), 4.3 (m, 2H), 3.2 (m, 2H), 2.8 (m, 2H), 2.5 (m, 1H shouldering on DMSO peak), 1.8 (m, 2H), 1.7 (m, 2H) A 500 mL round bottom flask equipped with a magnetic stir bar The volatiles were removed by rotary evaporation the crude oil was dissolved in ethyl acetate washed with saturated sodium bicarbonate solution (3×200 mL) The organic phase was dried over Na2SO4 filtered concentrated

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

Procedure: A 500 mL round bottom flask equipped with a magnetic stir bar was charged with 1,1-di methylethyl-4-({[(2,4-dichlorophenyl)methyl]amino}carbonyl)-1-piperidinecarboxylate (27.6 g, 71.2 mmol) and DCM (117 mL) at room temperature. Trifluoroacetic acid (117 mL) was added slowly, and the reaction was maintained at room temperature for 1 hour after which time LC/MS determined that the reaction was complete (Rt=6.03 min and m/e 287 [M+1]+). The volatiles were removed by rotary evaporation and the crude oil was dissolved in ethyl acetate and washed with saturated sodium bicarbonate solution (3×200 mL). The organic phase was dried over Na2SO4, filtered and concentrated to give 13.5 g of the title compound (47 mmol, 66%) as a pale yellow solid. MS (ES) m/e 287 [M+H]+. 1H NMR (400 MHz, DMSO-D6) □ 8.6 (m, 1H), 7.4 (d, 1H), 7.3 (d, 1H), 4.3 (m, 2H), 3.2 (m, 2H), 2.8 (m, 2H), 2.5 (m, 1H shouldering on DMSO peak), 1.8 (m, 2H), 1.7 (m, 2H) A 500 mL round bottom flask equipped with a magnetic stir bar The volatiles were removed by rotary evaporation the crude oil was dissolved in ethyl acetate washed with saturated sodium bicarbonate solution (3×200 mL) The organic phase was dried over Na2SO4 filtered concentrated