tert-butyl (3R)-3-aminopiperidine-1-carboxylate → (R)-tert-butyl 3-(5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-thiadiazol-2-ylamino)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A yellow solution of 2-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-5-(methylsulfonyl)-1,3,4-thiadiazole (177.5 mg, 0.284 mmol) and (R)-tert-butyl 3-aminopiperidine-1-carboxylate (Small Molecules, Inc., Hoboken, N.J.; 0.251 mL, 1.296 mmol) in dioxane (2.0 mL) was heated in an open microwave vial at 90° C. for 2 d. The resulting solid residue was taken up in N-methyl-2-pyrrolidinone (0.4 mL) and heated under argon at 120° C. for 2.5 days. The mixture was then diluted with DCM (10 mL), concentrated onto silica gel, and chromatographically purified (silica gel, 0-100% EtOAc/Hex) to provide (R)-tert-butyl 3-(5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-thiadiazol-2-ylamino)piperidine-1-carboxylate (98.0 mg, 0.142 mmol, 50%) as a yellow oil: MS (ESI, pos. ion) m/z: 689.2 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.80 (1H, s), 8.07 (1H, s), 8.06 (1H, d, J=8.2 Hz), 7.93 (1H, d, J=8.7 Hz), 7.82 (2H, d, J=8.4 Hz), 7.62 (1H, t, J=7.8 Hz), 7.28 (2H, d, J=8.0 Hz), 7.24 (2H, s), 6.63 (1H, d, J=8.2 Hz), 5.55 (1H, dt, J=12.0, 5.9 Hz), 4.40 (1H, d, J=6.1 Hz), 3.61-3.74 (2H, m), 3.47-3.57 (2H, m), 3.36-3.45 (2H, m), 3.30 (2H, m), 2.35 (3H, s), 1.47 (9H, s), 1.44 (6H, br. s.).

Provenance & Evidence