Potassium Carbonate → 1-[4-(3,4-Dichlorophenoxy)-3-methylaminomethyl-phenyl]-1H-pyrazol-3-ylamine dihydrochloride

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Reaction Steps

Under N2 in a flame-dried 15 mL round bottomed flask, fitted with a magnetic stirrer were placed 318 mg (0.88 mmol) of 5-bromo-2-(3,4-dichlorophenoxy)-N-methylbenzylamine (title compound of Example 15), 1.50 g (18 mmol) of 3-aminopyrazole, 56 mg (0.88 mmol) of copper powder and 122 mg (0.88 mmol) of potassium carbonate. The mixture was heated to 130° C. for a total of one hour, cooled and stirred at room temperature overnight. The tarry residue was partitioned between EtOAc and dilute aqueous EDTA (ethylenediaminetetraacetic acid), the organic layer was washed with water and saturated aqueous NaCl, then dried over Na2SO4. After filtration the solvent was removed in vacuo to give an oil, 287 mg, which was eluted on silica gel with a gradient system of NH4OH:CH3OH:CHCl3 (from 2:2:96 to 2:10:88). The product fractions were concentrated to an oil (110 mg) which was dissolved in 25 mL EtOAc and treated with 0.6 mL of 1 N HCl in Et2O. The solids which precipitated were filtered, washed with a small amount of Et2O and dried under vacuum to give 60 mg of the title product, m.p. 225-233° C.

Provenance & Evidence