反应详情

To a solution of 3-tert-butoxycarbonyl-7-chloro-6-[5-(cyclopropylmethyl-amino)-[1,3,4]thiadiazol-2-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.082 g, 0.171 mmol) in anhydrous DCM (3.5 mL) at room temperature add trifluoroacetic acid (3.5 mL) and stir the solution at room temperature overnight. Concentrate in. vacuo and elute the residue through a SCX column (20 g). Dissolve the residue in DCM, load the solution on to a RediSep® column (12 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 90:10 DCM/2M ammonia in methanol over 33 min; 35 mL/min) to afford 7-chloro-6-[5-(cyclopropylmethyl-amino)-[1,3,4]thiadiazol-2-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.051 g, 78%). MS (ES+) m/z: 381.1 (M+H)+. To a solution of 7-chloro-6-[5-(cyclopropylmethyl-amino)-[1,3,4]thiadiazol-2-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.044 g, 0.116 mmol) in absolute ethanol (5 mL), add succinic acid (0.014 g, 0.116 mmol). After acid dissolves, concentrate the reaction mixture in vacuo. Combine the residue with MTBE, concentrate in vacuo several times and dry under high vacuum at room temperature overnight to obtain the title compound (0.058 g, 100%) as a white foam. MS (ES+) m/z: 381.0 (M+H)+.

1. concentrationConcentrate in
2. washvacuo and elute the residue through a SCX column (20 g)
3. dissolutionDissolve the residue in DCM
4. customload the solution on to a RediSep® column (12 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 90:10 DCM/2M ammonia in methanol over 33 min; 35 mL/min)