Diisopropylethylamine → HCID 136346361, compound

Participants

Reaction Steps

To a solution of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate (77 mg, 0.124 mmol) in anhydrous N,N-dimethylformamide (1 mL) was added at room temperature (S)-4-Boc-morpholine-3-carboxylic acid (26.2 mg, 0.113 mmol), followed by N,N-diisopropylethylamine 0.059 mL, 0.339 mmol) and finally a solution of N-(1-{[3-(aminomethyl)phenyl]methyl}-4-hydroxy-1H-indazol-3-yl)-5-chloro-2-thiophenesulfonamide (formate salt) (for a preparation see intermediate 15) ((56 mg, 0.113 mmol) in anhydrous N,N-dimethylformamide (2 mL) and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was partitioned between saturated aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic layer was separated, washed with brine:water (1:1), passed through a hydrophobic frit and evaporated in-vacuo. The was treated with hydrogen chloride (4M solution in 1,4-dioxane) (1 mL) and then added methanol (˜4 mL) until the reaction was in solution. Reaction stirred at room temperature for 2 hours. The reaction mixture was evaporated in-vacuo and the residue was dissolved in MeOH/DMSO (1 mL) and purified by Mass Directed AutoPreparative HPLC (MDAP) on (Sunfire C18 column Method A) eluting with solvents A/B (A: 0.1% v/v solution of formic acid in water, B: 0.1% v/v solution of formic acid in acetonitrile) using a method B over 25 min. Appropriate fractions were combined and evaporated in-vacuo to yield the title compound as a colourless oil (13 mg, 19%). LCMS (System B) RT=1.63 min, ES+ve m/z 562/564 (M+H)+.

Provenance & Evidence