Triethylamine → HCID 67540456, compound

Participants

Reaction Steps

The 4-piperazin-1-yl-1H-pyrazolo[3,4-d]pyrimidine bis-hydrochloride salt (60 mg, 0.22 mmol), HOBt (29 mg, 0.22 mmol), EDCI (46 mg, 0.24 mmol), and 4-tert-butoxycarbonylamino-2-(2-chlorophenyl)-butyric acid [prepared by procedures described in Example 61 (68 mg. 0.22 mmol)] were suspended/dissolved in 1.5 mL of DMF then treated with triethylamine (121 μL, 0.87 mmol). The mixture was allowed to stir for four hours to completion then partitioned between ethyl acetate and diluted NaHCO3 solution. The aqueous was extracted with ethyl acetate, and the organics were combined. The organic was washed with water, brine, separated, dried over MgSO4, filtered, and concentrated in vacuo. The residue was dissolved in 1 mL of 1,4-dioxane and treated with 1 mL of 4M HCl in 1,4-dioxane. The solution stirred overnight to completion at room temperature and diluted with diethyl ether to afford a precipitate. This material was broken up to afford a suspended granular solid which was stirred for 30 minutes. The suspension was filtered, washed with diethyl ether, and dried over a stream of nitrogen to afford the 4-amino-2-(2-chlorophenyl)-1-[4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)-piperazin-1-yl]-butan-1-one bis-hydrochloride salt as a tan solid (69.2 mg, 67%). 1H NMR (D6O, 400 MHz) δ 8.52 (brs, 1H), 8.31 (s, 1H), 7.40 (d, J=7.2 Hz, 1H), 7.12 (m, 3H), 4.42 (t, J=6.8 Hz, 1H), 4.11 (m, 1H), 3.98 (m, 3H), 3.70 (m, 2H), 3.61 (m, 1H), 3.41 (m, 1H), 2.96 (m, 1H), 2.80 (m, 1H), 2.21 (m, 1H), 1.94 (m, 1H). LCMS (APCI+) m/z 400 [M+H]+; Rt=1.52 min.

Provenance & Evidence