The acetylene compound 92.5mg (0.3 mmol) and CuI 114.5mg (0.6mmol) was suspended in anh. dimethylacetamide 0.8mL in a 25mL14/20 round flask equipped with a straight stopcock. The mixture was degassed by highvac/Ar purge. Barton base 0.15mL (0.75mmol, Fluka) was added through the stopcock and the mixture was stirred at 135-140C oil bath under Ar in a closed flask for 3 hours. The mixture was cooled to RT, methanol 1mL was added followed by TMS-CN 0.25mL. The mixture was diluted with dichloromethane 10mL, sonicated for 10 min and then stirred at RT for 1 hour. The precipitated CuCN was removed by filtration through a pad of silica. The silica was washed with 50mL of a 10:1 mixture of dichloromethane with methanol. The filtrates were evaporated and the residue was dried on highvac. The crude product was purified on a column of silica (35g) in EtOAc gradient in dichloromethane, 10 to 30% of EtOAc (in 45 min, 20mL/min). Y= 77mg(83%) of a light tan solid
1H(CDCl3, 400MHz):8.330(br s, 1H), 7.393(m, 2H), 7.298(m, 2H), 7.223(m, 1H), 6.025(s, 1H), 5.707(br s, 1H), 4.677(s, 2H), 4.071(q, 7.0Hz, 2H), 2.635(t, 7.8Hz, 2H), 1.686(m, 2H), 1.453(m, 2H), 1.280(t, 7.0Hz, 3H), 0.973(t, 7.4Hz, 3H)
The above procedure was succesfully used to cyclize a large number of diaminopyrimidine acetylenes with excellent yields (82 to 96%Y). Various substituent groups on amines and Phe, Bu, H on acetylene were tolerated. Only TMS-protected acetylene compounds failed to provide diazaindoles but the deprotected acetylenes (R=H) cyclized smoothly.
Barton base is a low-boiling strong base. It serves here both as a copper ligand and a base – it keeps things soluble and it deprotonates the aminopyrimidine NH. (I have not tried other bases like DBU but the reaction works even without base – the reaction was slower and formation of voluminous precipitate was a complication). Since the product binds strongly to Cu, cyanide excess was used in the workup to break the complex. Trimethylsilyl cyanide is very poisonous, it has to be handled with gloves in the hood.