Diisopropylethylamine → ZD6021

Participants

Reaction Steps

A stirred solution containing 3-cyano-1-naphthoic acid (0.1 g, 0.5 mmol), N,N-diisopropylethylamine (0.16 g, 1.26 mmol), and dry DCM (2.5 mL) was treated with a solution of tetramethylfluoroformamidinium hexafluorophosphate (TFFH) (0.16 g, 0.60 mmol) in dry DCM (1.0 mL). After 10 min, a solution containing N-[(S)-2-(3,4-dichlorophenyl)-4-[4-[(S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methylamine (0.22 g, 0.5 mmol) and dry DCM (0.6 mL) was added, and the solution stirred for 60 h, then diluted with DCM and 1M aqueous acetic acid. After mixing, the layers were allowed to separate, the organic layer was removed, and the aqueous layer was extracted with additional DCM (2×). The organic extracts were combined, washed (saturated NaHCO3), dried (Na2SO4), filtered, and the DCM evaporated in vacuo. The residue was purified by chromatography (0-10% CH3OH in DCM) to give the title compound (0.25 g) as a white, foamy residue. MS: m/z 632 (M+H). The product was converted to the citrate salt and isolated by filtration from Et2O to afford the N-[(S)-2-(3,4-dichlorophenyl)-4-[4-[(S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methyl-3-cyano-1-naphthamide citrate hydrate (1:1:0.75) (290 mg) as a white solid. MS: m/z 632 (M+H). Analysis for C35H35Cl2N3O2S C6H8O7.0.75 H2O: calculated: C, 58.74; H, 5.35; N, 5.01. found: C, 58.74; H, 5.24; N, 5.02. The title compound could also be converted, in similar maimer, to the citrate hydrate (1.0:1.0:1.0).

Provenance & Evidence