Diisopropylethylamine → N1-[(3-{[3-{[(5-Chloro-2-thienyl)sulfonyl]amino}-4-(methyloxy)-1H-indazol-1-yl]methyl}phenyl)methyl]-N2,2-dimethylalaninamide formate

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Reaction Steps

To a solution of N-Boc-N,2-dimethylalanine (174 mg, 0.801 mmol) in anhydrous THF (8 mL) was added dropwise at room temperature 1-chloro-N,N,2-trimethylpropenylamine (0.106 mL, 0.801 mmol) and the resulting mixture was stirred for 30 min. N-[1-{[3-(aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide hydrochloride (for a preparation see Intermediate 4) (200 mg, 0.4 mmol), followed by N,N-diisopropylethylamine (0.209 mL, 1.20 mmol) were then added and the reaction mixture was stirred at room temperature for 90 min (heterogeneous reaction). A further 8 mL of anhydrous tetrahydrofuran and 70 μL of N,N-diisopropylethylamine was added in order to try to improve solubility. The reaction mixture was stirred at room temperature for 30 min and then evaporated in-vacuo and partitioned between saturated aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic layer was separated, passed through a hydrophobic frit and evaporated in-vacuo to yield a cream oil. The residue (286 mg) was dissolved in MeOH:DMSO (1:1) (3×1 mL) and purified by MDAP on (Sunfire C18 column 150 mm×30 mm i.d. 5 μm packing diameter at ambient temperature) 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) over 25 min. Appropriate fractions were combined and evaporated in-vacuo to yield the title compound as a clear oil (211 mg, 87%). LCMS (System B) RT=1.75 min, ES+ve m/z 562/564 (M+H)+.

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