N-(tert-butoxycarbonyl)glycine → tert-butyl[2-({4-[3-carbamoyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazolin-1-yl]cyclohexyl}amino)-2-oxoethyl]carbamate

Participants

Reaction Steps

30 mg (0.084 mmol) of 1-(4-aminocyclohexyl)-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide hydrochloride were dissolved in 2 ml of dimethyl acetamide. To the obtained solution 21 mg (0.126 mmol) of N-(tert-butoxycarbonyl)glycine, 60 μl (0.336 mmol) of DIPEA, 40 mg (0.126 mmol) of TBTU were added. The mixture was stirred at room temperature for 18 hours, the solution was portioned between ethyl acetate and saturated aqueous solution of NaHCO3, the organic layer was washed with brine, dried over Na2SO4 and evaporated under vacuum. The crude was purified by silica gel chromatography (DCM/MeOH/NH4OH 95/5/0.1) to provide tert-butyl[2-({4-[3-carbamoyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazolin-1-yl]cyclohexyl}amino)-2-oxoethyl]carbamate 35 mg (81%) as a white solid. 1H NMR (401 MHz, DMSO-d6) δ 9.47 (s, 1H), 8.27 (d, J=8.67 Hz, 1H), 7.78 (d, J=6.35 Hz, 1H), 7.74 (d, J=8.67 Hz, 1H), 7.64 (br. s., 1H), 7.55 (br. s., 1H), 6.86 (t, J=5.86 Hz, 1H), 6.00 (br. s., 1H), 3.96 (d, J=2.56 Hz, 1H), 3.62 (d, J=5.61 Hz, 2H), 2.72 (s, 3H), 2.23-2.36 (m, 2H), 1.91-2.11 (m, 4H), 1.68-1.82 (m, 2H), 1.38 (s, 9H).

Provenance & Evidence