Triacetoxyperiodinane → 5-(2-((2S,3S)-2-amino-4-hydroxy-3-(4-(trifluoromethyl)phenyl)pentylamino)thiazol-5-yl)indolin-2-one

Participants

Reaction Steps

The title compound was synthesized in a manner similar to Example 158 starting with tert-butyl (2S,3S)-1-(5-bromothiazol-2-yl-(Boc)-amino)-4-hydroxy-3-(4-(trifluoromethyl)phenyl)butan-2-ylcarbamate as shown in Scheme 36. After an oxidation with Dess-Martin periodinane, tert-butyl (2S,3S)-1-(5-bromothiazol-2-yl-(Boc)-amino)-4-hydroxy-3-(4-(trifluoromethyl)phenyl)butan-2-ylcarbamate was converted to tert-butyl (2S,3S)-1-(5-bromothiazol-2-yl-(Boc)-amino)-4-oxo-3-(4-(trifluoromethyl)phenyl)butan-2-ylcarbamate. The aldehyde tert-butyl (2S,3S)-1-(5-bromothiazol-2-yl-(Boc)-amino)-4-oxo-3-(4-(trifluoromethyl)-phenyl)butan-2-ylcarbamate reacted with methylmagnesium bromide to generate tert-butyl (2S,3S,4S)-1-(5-bromothiazol-2-yl-(Boc)-amino)-4-hydroxy-3-(4-(trifluoromethyl)phenyl)pentan-2-ylcarbamate as the intermediate for the Suzuki reaction with 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indolin-2-one leading to the final product. MS m/z: 477 (M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.68 (d, J=8.22 Hz, 2H) 7.54 (d, J=8.22 Hz, 2H) 7.34 (d, J=1.56 Hz, 1H) 7.26 (dd, J=8.12, 1.86 Hz, 1H) 6.87 (d, J=8.22 Hz, 1H) 4.39 (dd, J=9.00, 6.06 Hz, 1H) 3.77-3.82 (m, 1H) 3.41 (dd, J=13.69, 5.28 Hz, 1H) 3.37 (s, 3H) 3.20 (dd, J=13.50, 8.02 Hz, 1H) 2.92 (dd, J=9.00, 3.52 Hz, 1H) 1.08 (d, J=6.26 Hz, 3H).

Provenance & Evidence