Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → (S)-3-Cyclohexyl-N-(2-methyl-pyrimidin-4-yl)-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide

Participants

Reaction Steps

BOP coupling of (S)-3-Cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (prepared in Example 1, Step A; 287 mg; 1.00 mmol) and 2-aminopyridine N-Oxide (110 mg; 1.00 mmol) in a manner similar to that used for the preparation of (R)-3-cyclohexyl-2-( 1-oxo-1, 3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide (outlined in Example 9, Step B) provided after flash chromatography (Merck Silica gel 60, 230-400 mesh, eluent: 2% methanol/ethyl acetate) 340 mg (55%)of (S)-N-(pyridin-N-oxide-2-yl)-3-cyclohexyl-2-( 1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide as an off white foam. The product did not appear to be pure by NMR and so it was further purified by reverse phase HPLC (Rainin Dynamax SD-1instrument) using a gradient of 10% acetonitrile/water/0.1% trifluoroacetic acid to 100% acetonitrile on a C18 column to provide 188 mg of pure (S-3-Cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-(1-oxy-pyridin-2-yl)-propionamide: ES-LRMS m/e calcd for C22H25N3O3 (M++H+) 380, found 380.

Provenance & Evidence