Thionyl Chloride → HCID 67521073, compound

Participants

Reaction Steps

A solution of 1-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol (500 mg, 1.59 mmol) dissolved in 15 mL of anhydrous CH2Cl2 was treated with thionyl chloride (232 mL, 3.18 mmol). After 30 minutes, the reaction mixture was concentrated under reduced pressure. The resulting material was concentrated from ethanol and then dissolved in 15 mL of TFA. The mixture was placed in pressure flask and treated with 250 mg of PtO2. The mixture was then shaken under H2 at 50 PSI (3.4×105 Pa) for 3 hours. The reaction mixture was filtered through a pad of CELITE filter agent. The pad was rinsed with CH2Cl2 and 2-propanol and the combined filtrates were concentrated under reduced pressure to give a syrup. The syrup was dissolved in 50 mL of hot ethanol and crystals formed upon cooling. The crystals were isolated by filtration and were then partitioned between dilute NH4OH solution (25 mL) and CH2Cl2 (25 mL). The organic portion was washed with additional dilute NH4OH solution (2×), H2O and brine. The organic portion was concentrated to give a syrup. Crystallization from HCl in ethanol gave the title compound as a yellow powder, m.p. 222-227° C. 1H NMR (300 MHz, DMSO-d6) δ 7.87 (s, 2H), 4.74 (s, 2H), 4.18 (s, 2H), 3.50 (q, J=7.0 Hz, 2H), 3.06 (t, J=5.1 Hz, 2H), 2.71 (t, J=6.2 Hz, 2H), 2.08 (m, 2H), 1.17 (s, 6H), 1.14 (t, J=7.0 Hz, 3H); 13C NMR (125 MHz, DMSO-d6) δ 150.5, 143.9, 132.8, 121.3, 119.5, 119.3, 65.4, 63.7, 54.5, 54.4, 22.1, 20.9, 20.7, 14.8; MS (ESI) m/z 302 (M+H)30; Anal. calcd for C16H23N5O.HCl: C, 56.88; H, 7.16; N, 20.73; Cl, 10.51. Found: C, 56.61; H, 8.09; N, 20.51; Cl, 10.88.

Provenance & Evidence