1-Chloro-4-iodobenzene → HCID 131729465, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (R)-7-(quinuclidin-3-yl)-7,8-dihydropyrazolo[3,4,5-de]isoquinolin-6(2H)-one (100 mg, 0.35 mmol) from Step C of Example 16, 1-chloro-4-iodobenzene (100 mg, 0.42 mmol), copper (I) iodide (3.3 mg, 0.02 mmol), N,N-dimethylcyclohexane-1,2-diamine (11 μL, 0.07 mmol), potassium phosphate tribasic (144 mg, 0.74 mmol) and toluene (1 ml) was placed in a sealed tube and degassed with nitrogen for 2 min. The reaction was heated at 110° C. for 24 h and, after cooling the solution to room temperature, the solvent was evaporated and the residue was purified by preparative TLC (silica gel, 90:10:1 dichloromethane/methanol/concentrated ammonium hydroxide) and preparative HPLC. The resultant compound was then treated with 1.25 M HCl in methanol to afford (R)-2-(4-chlorophenyl)-7-(quinuclidin-3-yl)-7,8-dihydropyrazolo[3,4,5-de]isoquinolin-6(2H)-one, hydrochloride salt (2.5 mg, 2%) as a light yellow solid. 1H NMR (500 MHz, D2O) δ 7.52 (d, J=8.5 Hz, 1H), 7.44 (dd, J=8.5, 7.0 Hz, 1H), 7.37 (d, J=7.0 Hz, 1H), 7.20-7.15 (m, 4H), 4.95 (d, J=17.5 Hz, 1H), 4.80 (d, J=18.0 Hz, 1H), 4.65-4.58 (m, 1H), 3.78 (t, J=10.5 Hz, 1H), 3.49-3.43 (m, 2H), 3.33-3.25 (m, 3H), 2.45 (s, 1H), 2.20-2.15 (m, 1H), 2.04-1.94 (m, 3H); MS (ESI+) m/z 393 (M+H); HPLC 98.4% (AUC), tR 15.66 min.

Provenance & Evidence