tert-Butyldimethylsilane → HCID 58997411, compound

Participants

Reaction Conditions

Reaction Steps

The title H compound, (S)-2-((S)-2-acetylamino-3-phenyl-propionylamino)-3-{3-[5-(4-methoxy-benzyl)-1,1,4-trioxo-1,2,5-thiadiazolidin-2-ylmethyl]-phenyl}-N-pentyl-propionamide (77 mg, 0.111 mmol) is dissolved in TFA (2.2 mL) containing t-butyl-dimethylsilane (0.055 mL, 0.33 mmol) and heated at 80° C. for 3.75 h. The reaction is concentrated under nitrogen stream and the resulting tan solid is taken up in 60% MeCN in water. Water (1 mL) is added, and the mixture is filtered through a 0.1 micron Acrodisc filter. The filtrate is loaded onto a preparative reverse phase HPLC column (YMC CombiPrep Pro C18, 50×20 mm I.D., particle size S-5 micron, 12 nM) in 7 aliquots and eluted at 30 mL/min with a gradient of 90:10 (water containing 0.1% TFA: MeCN) to 10:90 over 5 min. Then held at 10:90 until 7 min. Fractions containing product are combined and concentrated on a Savant Speedvac to yield the product still containing an unknown impurity by HPLC. This is chromatographed again, using the same column, but a different elution gradient, 90:10 (0.1% TFA in water: MeCN) to 40:60 over 14 min. Fractions containing product are combined and concentrated to yield (S)-2-acetylamino-N-{(S)-1-pentylcarbamoyl-2-[3-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-ylmethyl)-phenyl]-ethyl}-3-phenyl-propionamide as a white film: [M+1]+=572.

Provenance & Evidence