Phosgene → 5-Isocyanatoisoquinoline

Participants

Reaction Conditions

Reaction Steps

A solution of phosgene (20% in toluene, 5.8 ml, 11 mmol) was added to 50 ml methylene chloride and cooled to 0° C. 4-Dimethylaminopyridine (2.86 g, 23.4 mmol) in 30 ml methylene chloride was added dropwise. A thick white suspension formed. A solution of 5-aminoisoquinoline (1.44 g, 10 mmol) in 30 ml methylene chloride was then added dropwise to this suspension. The reaction was allowed to warm to ambient temperature and stirred overnight. At the end of this time, a solution formed, and the solvent was removed under reduced pressure. The residue was triturated with 50 ml diethyl ether to give an approximately 0.1 M solution of 5-isocyanato-isoquinoline. 32 ml of this solution was added to Example 35E (0.70 g, 3.2 mmol), and the reaction stirred overnight. The precipitate that formed was collected by filtration to give 0.43 g of Example 35F. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.28 (s, 1 H), 8.65 (s, 1 H), 8.54 (d, J=6.10 Hz, 1 H), 8.31-8.37 (m, 1 H), 7.90 (d, J=6.10 Hz, 1 H), 7.76 (d, J=8.14 Hz, 1 H), 7.55-7.66 (m, 2 H), 7.24-7.29 (m, 1 H), 7.13-7.22 (m, 2 H), 5.03 (m, 1 H) 4.38 (m, 1 H) 4.27 (m, 3.22 Hz, 1 H) 2.14-2.26 (m, 1 H) 2.08 (m, 1 H). MS (ESI) m/e 388 (M+H)+.

Provenance & Evidence