(1R,3R)-Methyl 1-(benzo[d][1,3]dioxol-5-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate hydrochloride

Uses

(1R,3R)-Methyl 1-(benzo[d][1,3]dioxol-5-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate hydrochloride is a key pharmaceutical intermediate used in the synthesis of the drug tadalafil. Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor primarily used to treat erectile dysfunction and benign prostatic hyperplasia in men.

Preparation

D-tryptophan methyl ester hydrochloride and piperonal chloride dissolved in redistilled tetrahydrofuran and then added trifluoroacetic acid. Stir the reaction at 30 ° C for 10 h under the protection of nitrogen. Add sodium triacetoxyborohydride and continue the reaction for 3 hours. After the reaction is monitored by a TLC plate, the reaction solution is concentrated to about 10 mL, deionized water is added, and extracted with ethyl acetate twice. Saturated sodium chloride was washed twice, and dried under reduced pressure to obtain (1R,3R)-Methyl 1-(benzo[d][1,3]dioxol-5-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate hydrochloride. The yield was 86.95%, the purity was 98.76%.