(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidine → (S)-tert-butyl 1-(5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-thiadiazol-2-yl)pyrrolidin-3-ylcarbamate

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A yellow solution of 2-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole (168.4 mg, 0.296 mmol) and (35)-(−)-3-(tert-butoxycarbonylamino)pyrrolidine (TCI America, Portland, Oreg.; 165 mg, 0.888 mmol) in dioxane (1.0 mL) was heated in an open microwave vial at 90° C. for 2 days. Chromatographic purification of the resulting dry residue (silica gel, 0-100% EtOAc/Hex) furnished (S)-tert-butyl 1-(5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-thiadiazol-2-yl)pyrrolidin-3-ylcarbamate (180 mg, 0.267 mmol, 90%) as a light-yellow solid: MS (ESI, pos. ion) m/z: 675.1 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.80 (s, 1H), 8.07 (s, 2H), 7.94-7.99 (m, 1H), 7.82 (d, J=8.2 Hz, 2H), 7.62 (t, J=7.8 Hz, 1H), 7.28 (d, J=7.4 Hz, 1H), 7.22-7.25 (m, 2H), 6.63 (d, J=8.2 Hz, 1H), 5.57 (spt, J=6.2 Hz, 1H), 4.72 (br. s., 1H), 4.40 (br. s., 1H), 3.84 (dd, J=10.4, 5.9 Hz, 1H), 3.68-3.75 (m, 1H), 3.60-3.68 (m, 1H), 3.41-3.55 (m, 1H), 3.45 (m, J=10.4, 3.5 Hz, 1H), 2.35 (s, 3H), 1.46 (s, 9H), 1.45 (br. s., 6H).

Provenance & Evidence