Dimethylformamide → 1-Piperidinecarboxamide

The synthesis of compound 61 was carried out according to scheme 13 beginning with commercially available pyrazolo[1,5-a]pyridine-3-carboxylic acid and by following the procedure outlined in example 1, part C, step 2 and subsequent steps though step E, part 1. The thiazole 5-position was left unfunctionalized by omitting part D, step 3 to obtain with the carboxylic acid 57. To carboxylic acid 57 (725 mg, 2.96 mmol) in DMF (30 mL) was added BOP (392 mg, 8.87 mmol) and piperidine (2.93 mL, 29.6 mmol). The reaction was stirred at ambient temperature for 48 hrs after which time the reaction was diluted with water and dichloromethane. The organic was washed with water before concentration. The resultant residue was purified by column chromatography (silica gel, 0-60% ethyl acetate in hexanes, linear gradient) to yield the piperidine amide (739 mg, 2.366 mmol, 80% yield). The amide (420 mg, 1.34 mmol) was dissolved in dichloromethane (1.3 mL) was treated with potassium nitrate (136 mg, 1.344 mmol) and sulfuric acid (215 μL, 4.03 mmol). The reaction mixture was stirred at RT until complete, as judged by LCMS analysis. The reaction was quenched with 1N potassium hydroxide in methanol, then diluted with water, before extracting with dichloromethane. The organic layer was evaporated to dryness and taken up in methanol. The product was collected by filtration and was dried under reduced pressure to yield compound 58 (225 mg, 0.630 mmol, 46.8% yield).

1. washThe organic was washed with water before concentration
2. customThe resultant residue was purified by column chromatography (silica gel, 0-60% ethyl acetate in hexanes, linear gradient)

ORD record

ord-8223b432f30045de91758e04eb6055de

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08518911B2