Toluene → Ethyl 4-(3-(benzyloxycarbonylamino)-2-methylphenyl)-6-morpholino-9H-pyrido[3,4-b]indole-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of benzyl 3-(2-amino-1-(5-morpholino-1H-indol-3-yl)ethyl)-2-methylphenylcarbamate (0.713 g, 1.471 mmol) and 50% ethyl 2-oxoacetate (0.583 mL, 2.94 mmol)/toluene in 1,4-dioxane (61.3 mL) was added 4 N hydrochloric acid/1,4-dioxane (0.736 mL, 2.94 mmol)/dioxane under nitrogen. After stirring overnight, more 50% ethyl 2-oxoacetate (0.583 mL, 2.94 mmol) was added. After 2 hr, the reaction was heated to 40° C. After another 2 hr, the reaction was cooled to room temperature, concentrated in vacuo, and dissolved in water (50 mL) and EtOAc (50 mL). The mixture was basified with saturated NaHCO3 solution to pH ˜10. The layers were separated and the aqueous layer was extracted with EtOAc (3×50 mL). The organic layers were combined, washed with brine, dried over MgSO4, and concentrated in vacuo to give crude product used in subsequent step. This was added to 10% Pd/C (0.377 g, 0.354 mmol) in p-xylene (39.4 mL), and the reaction was heated at 125° C. After 9 h, the reaction was cooled to room temperature, filtered through a wad of CELITE®, rinsed with EtOAc, and the filtrate was concentrated in vacuo. The residue was dissolved in EtOAc (100 mL), washed with brine (25 mL), dried over MgSO4, and concentrated in vacuo. The residue was purified by flash chromatography using an ISCO 40 g column eluting with 0-50% EtOAc/CH2Cl2 to give the desired product (0.1558 g, 0.276 mmol, 23.4% yield) as a light orange foam.

Provenance & Evidence