Diisopropylethylamine → {(1S,3R)-3-ethoxy-1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-butyl}-carbamic acid t-butyl ester

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Reaction Steps

(2S,4R)-2-t-butoxycarbonylamino-4-ethoxy-pentanoic acid (273 mg, 1.04 mmol) was mixed with 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 194.6 mg, 1.25 mmol) in N,N-dimethylformamide (10 mL). benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (695 mg, 1.57 mmol) and N,N-diisopropylethylamine (0.4 mL) was added at 0° C. The mixture was stirred at room temperature overnight. Solvents were evaporated and the residue was extracted with ethyl acetate and saturated sodium chloride solution. Solvents were evaporated and the crude material was purified by flash column chromatography (silica gel, 10-80% ethyl acetate/hexanes) to afford {(1S,3R)-3-ethoxy-1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-butyl}-carbamic acid t-butyl ester (306 mg, 73%) as a white solid: LR-ES-MS m/z calculated for C19H34N4O5 [M]+ 398, observed [M+H]+ 399; 1H NMR (300 MHz, CDCl3, plus drops of CD3OD) δ ppm 1.08-1.15 (m, 12H), 1.37 (s, 9H), 1.72-1.94 (m, 2H), 3.35-3.60 (m, 3H), 3.89 (s, 2H), 4.20 (m, 1H), 6.48 (br. s., 1H).

Provenance & Evidence