Tris(hydroxymethyl)aminomethane → Hydrochloric Acid

Participants

Reaction Steps

(R)-Tert-butyl 6-(2-((2-(3-amino-4-fluorophenyl)-2-(triethylsilyloxy)ethyl)(tert-butoxycarbonyl)amino)ethoxy)-3-chloroindazole-1-carboxylate-CH2Cl2 solution [0.5 mL; solution obtained by dissolving (R)-tert-butyl 6-(2-((2-(3-amino-4-fluorophenyl)-2-(triethylsilyloxy)ethyl)(tert-butoxycarbonyl)amino)ethoxy)-3-chloroindazole-1-carboxylate (480 mg) which can be prepared according to the method described in Reference example 70, etc. in dehydrated CH2Cl2 (3.52 mL)] was added with dehydrated pyridine (42 μL), benzenesulfonyl chloride-CH2Cl2 solution [0.5 mL; solution obtained by dissolving benzenesulfonyl chloride (466.3 mg; manufactured by Wako Pure Chemical Industries, Ltd.) in dehydrated CH2Cl2 (4 mL)] and dehydrated CH2Cl2, and the mixture was shaken (600 min−1) overnight at room temperature. To the reaction solution, PS-Trisamine [300 mg (3.6 mmol/g); manufactured by Argonaut] was added and the mixture was shaken (600 min−1) for 5 hours at room temperature. The reaction solution was filtered and the solvent was evaporated by blowing nitrogen gas to the filtrate. The resulting residue was purified by column chromatography (“COLUMN-I”; methanol). The resulting purified product was dissolved in 1,4-dioxane (0.2 mL), added with 4 mol/L-hydrochloric acid-1,4 dioxane solution (1.5 mL), and then shaken (600 min−1) overnight at room temperature. To the reaction solution, nitrogen gas was blown to evaporate the solvent, and the resulting residue was added with MTBE to obtain suspension. Nitrogen gas was blown to the suspension to evaporate the solvent, and as a result, the title compound was obtained as a hydrochloride (40.7 mg).

Provenance & Evidence