Diisopropylethylamine → N-(2-amino-4-(tert-butyl)phenyl)-2-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)acetamide

Participants

Reaction Steps

A solution of 2-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)acetic acid and 4-tert-butylbenzene-1,2-diamine (89.4 mg, 0.545 mmol) in N,N-dimethylformamide (4.5 mL) was treated with N,N-diisopropylethylamine (0.261 mL, 1.50 mmol) dropwise followed by N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (259 mg, 0.681 mmol). The solution was allowed to stir at room temperature for 18 h during which time LCMS indicated the starting material had been consumed. The reaction mixture was concentrated under high vac. The residue was taken up in 30 mL ethyl acetate and 20 mL 1/1 H2O/sat NaHCO3 solution. The mixture was extracted and the aqueous phase was washed with 35 mL ethyl acetate. The combined organic phase was washed with two 20 mL portions of H2O, and 20 mL brine. The organic phase was dried over Na2SO4, filtered and concentrated to yield a tannish brown glass/stiff foam. The crude material was purified by flash chromatography (35 g silica gel; 4% 7N NH3 in CH3OH/CH2Cl2) to yield the title compound (272 mg, 82%) as a light tan glass/stiff foam which was a mixture of regioisomeric amides: MS (ESI+) for C41H53N7O6 m/z 728.8 (M+H)+; MS (ESI−) for C41H53N7O6 m/z 726.9 (M−H)−; HPLC purity >95%, (ret. time, 3.14, 3.17 min) two peaks observed due to amide regioisomers.

Provenance & Evidence