1,2-Dichloroethane → HCID 69642023, compound

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Reaction Steps

The mono HCl salt of EDC (0.86 g, 4.5 mmol, 1.5 equiv) was added to a suspension of 3-(5-(3,4-dimethoxy-phenyl)pyrimidin-2-yl)-propanoic acid (0.95 g, 3.3 mmol, 1.1 equiv), 3-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (0.64 g, 3.0 mmol), HOBT (0.61 g, 4.5 mmol, 1.5 equiv), and diisopropylethylamine (1.3 mL, 7. mmol, 2.5 equiv) in a 50 mL solvent (THF:DMF, 7:3). After stirring overnight at rt, the mixture was concentrated and the residue was dissolved in 50 mL ethyl acetate. The solution was poured into 50 mL of a saturated NaHCO3 solution and extracted thoroughly with ethyl acetate. The combined organic layers were washed with brine and water, dried (Na2SO4), and concentrated. The residue was purified by flash chromatography (0→10% MeOH in CHCl3). Clean fractions containing the desired product were combined and concentrated to give 3-({3-[5-(3,4-dimethoxy-phenyl)-pyrimidin-2-yl]-propionylamino}-methyl)-piperidine-1-carboxylic acid tert-butyl ester (1.22 g, 84%) as a dark brown solid. The solid was dissolved into CH2Cl2 (30 mL) and neat TFA (5 mL) added dropwise. After about 30 min, the solution was concentrated to an oil on the teflon dryvac, then under high vacuum. LCMS analysis indicated quantitative conversion to 3-[5-(3,4-dimethoxy-phenyl)-pyrimidin-2-yl]-N-piperidin-3-ylmethyl-propionamide 2c.

Provenance & Evidence