Piperidine → HCID 18511143, compound

Participants

Reaction Conditions

Reaction Steps

In a round-bottomed flask was added 2-amino-6-phenylpyrrolo[3,2-d]pyrimidin-4-ol (Example 66(d)) (0.26 g, 1.2 mmol) and phosphorus oxychloride (2.7 mL, 28.8 mmol). The mixture was heated in a 124° C. oil bath for 24 h, then excess POCl3 was removed in vacuo to afford a brown residue. Ice-cold water was added and the pH of the solution was adjusted to pH 8 (pH paper) by adding aqueous Na2CO3. The resulting precipitate was collected by filtration, washed with water and then dried in a vacuum oven at 40° C. to give a brown solid. This material was transferred to a round-bottomed flask and heated with piperidine (0.57 mL, 5.75 mmol) and dioxane (8 mL) in a 110° C. oil bath for 15 h. Most of the solvent was then evaporated in vacuo. Chloroform was added to the residue, and the orgainc layer was separated, washed with water, dried over Na2SO4 and concentrated in vacuo to give a brown foam. Purification by flash chromatography on silica gel with 100:2:1 CHCl3:MeOH:Et3N as eluent afforded 92 mg (27%) of the title compound as a tan solid. The above material (78 mg, 0.27 mmol) was dissolved in a minimal amount of CHCl3 and HCl (0.6 mL of a 1M soln in ether, 0.6 mmol) was added dropwise. The mixture was stirred at room temperature for 20 min, and the solvent was evaporated in vacuo to give a tan foam. Recrystallization from MeOH/H2O gave 26 mg (6%) of the title compound as off-white crystals. Mp: >300° C. (dec). 1H NMR (DMSO-d6; 500 MHz): δ 1.66-1.67 (m, 6), 3.97 (m, 4), 6.66 (s, 1), 7.32 (br s, 2), 7.45-7.53 (m, 3), 7.87 (d, 2, J=7.26), 11.53 (br s, 1), 12.51 (br s, 1); MS m/z: 294 (M+1), 292 (M−1). Anal. Calcd for C17H19N5.HCl.0.2H2O: C, 61.28%; H, 6.16%; N, 21.02%; Cl, 10.64%. Found: C, 61.28%; H, 6.15%; N, 21.06%; Cl, 10.78%.

Provenance & Evidence