Tris(hydroxymethyl)aminomethane → Hydrochloric Acid

Participants

Reaction Steps

A (R)-tert-butyl 6-(2-((2-(3-amino-4-chlorophenyl)-2-(triethylsilyloxy)ethyl)(tert-butoxycarbonyl)amino)ethoxy)-3-methylindazole-1-carboxylate-CH2Cl2 solution [0.5 mL; solution prepared by dissolving (R)-tert-butyl 6-(2-((2-(3-amino-4-chlorophenyl)-2-(triethylsilyloxy)ethyl)(tert-butoxycarbonyl)amino)ethoxy)-3-methylindazole-1-carboxylate (1.324 g) that can be produced by the method described in Reference Example 101 or the like in dehydrated CH2Cl2 (10 mL)], dehydrated pyridine (42 μL), a benzenesulfonyl chloride-CH2Cl2 solution [0.5 mL; solution prepared by dissolving benzenesulfonyl chloride (466.3 mg; manufactured by Wako Pure Chemical Industries, Ltd.) in dehydrated CH2Cl2 (4 mL)], and dehydrated CH2Cl2 were added, and the mixture was shaken (600 min−1) overnight at room temperature. PS-Trisamine [300 mg (3.6 mmol/g); manufactured by Argonaut Technologies, Inc.] was added to the reaction solution, and the mixture was shaken (600 min−1) for 5 hours at room temperature. The reaction solution was filtered, and nitrogen gas was blown into the filtrate to evaporate the solvent. The resulting residue was purified by column chromatography (“COLUMN-I”; methanol). The obtained purification product was dissolved in 1,4-dioxane (0.2 mL), and a 4 mol/L hydrochloric acid-1,4-dioxane solution (1.5 mL) was added thereto. The mixture was shaken (600 min−1) overnight at room temperature. Nitrogen gas was blown into the reaction solution to evaporate the solvent, and MTBE was added to the obtained residue to obtain a suspension. Nitrogen gas was blown into the suspension to evaporate the solvent, and thus the title compound was obtained in the form of hydrochloride (46.4 mg).

Provenance & Evidence