N'-((2R,3S)-2-(3-Chloro-4-cyano-2-ethylphenylamino)-3-hydroxybutanoyl)-4-cyanobenzohydrazide → 2-Chloro-4-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)-3-ethylbenzonitrile

Participants

Reaction Steps

To a solution of N′-((2R,3S)-2-(3-chloro-4-cyano-2-ethylphenylamino)-3-hydroxybutanoyl)-4-cyanobenzohydrazide (310 mg, 0.73 mmol) in anhydrous THF (20 mL) at room temperature was added 2-tert-butylamino-2-diethylamino-1,3-dimethyl perhydro-1,3,2-diazaphosphorine on polystyrene (2.2 mmol base/g) (1.0 g) followed by p-TSCl (167 mg, 0.88 mmol) and the mixture was stirred for 1 h. The mixture was filtered under suction and the residue washed with acetone (200 mL) followed by MeOH (200 mL). The filtrate was concentrated and subjected to flash column chromatography [EtOAc-hexanes (2:1)]. The fourth fraction was the desired 2-chloro-4-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)-3-ethylbenzonitrile (45 mg, 15%).). 1H NMR (500 MHz, acetone-d6, δ in ppm) 8.20 (d, J=8.6 Hz, 2H), 7.99 (d, J=8.6 Hz, 2H), 7.48 (d, J=8.6 Hz, 1H), 6.86 (d, J=8.6 Hz, 1H), 5.79 (d, J=8.3 Hz, 1H), 5.18 (dd, J=3.3 Hz, 8.3 Hz, 1H), 4.85 (d, J=5.1 Hz, 1H), 4.68-4.60 (m, 1H), 2.98-2.88 (m, 2H), 1.43 (d, J=6.4 Hz, 3H) and 1.2 (t, J=7.6 Hz, 3H).

Provenance & Evidence