1-Hydroxybenzotriazole → HCID 67973772, compound

Participants

Reaction Steps

A solution of 1-{5-[(S)-1-((S)-2-tert-butoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-pyridin-3-yl}-1H-indole-4-carboxylic acid ethyl ester (I-1A-1c: 2.5 g, 4.7 mmol) in TFA (2 mL) and CH2Cl2 (2 mL) was stirred at room temperature for 18 hours. More TFA (3.6 mL) was added. The mixture was stirred for 3 hours and concentrated under reduced pressure. To the resulting oily residue was added anhydrous. DMF, DIEA (7.6 mL, 44 mmol), Boc-L-valine (0.89 g, 4.4 mmol), HBTU (1.8 g, 4.8 mmol), and HOBT (0.74 g, 4.9 mmol). The mixture was stirred at room temperature overnight. To the reaction mixture was added more HBTU (0.83 g, 2.2 mmol), Boc-Me-Alanine (0.18 g, 0.87 mmol), and DIEA (2.3 mL, 13.1 mmol). Stirring continued at room temperature overnight. The reaction mixture was then diluted with EtOAc (200 mL) and washed with water (2×100 mL). The aqueous layer was extracted with EtOAc (50 mL) and the combined organic layers were washed with water again (2×25 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to give an oil. This oil was purified by silica gel column chromatography (0-100% EtOAc/heptane) to give the titled compound as a light yellow foam (1.7 g, 58% for 2 steps).

Provenance & Evidence