Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.
Procedure: 6-Bromo-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one. 3,5-Dibromopyrazin-2-amine (9.79 g, 38.7 mmol) was dissolved in dimethylsulfoxide (12 mL) with stirring in a 150 mL sealable vessel. Diisopropylethylamine (13.5 mL, 77.4 mmol) was added followed by 2-(tetrahydro-2H-pyran-4-yl)ethanamine (5.00 g, 38.7 mmol). Nitrogen was blown into the vessel to blow out air and the vessel was sealed. The resulting reaction mixture was stirred vigorously and heated at 100° C. for 16 h and then cooled to room temperature. 1,1′-Carbonyldiimidazole (9.41 g, 58.0 mmol) was added and the resulting mixture heated at 70° C. Nitrogen was blown into the vessel to blow out air and the vessel was sealed. The resulting reaction mixture was stirred vigorously and heated at 70° C. for 3 h and then cooled to room temperature. More 1,1′-carbonyldiimidazole (3.14 g, 19.4 mmol) was added and the resulting mixture heated at 70° C. for 3.5 h and then cooled to room temperature. The resulting mixture was diluted with ethyl acetate and poured into a separatory funnel containing water and 50% ethyl acetate in hexane. Solids formed while the separatory funnel was being shaken. The solids were collected by vacuum filtration, washed three times with water and twice with ethyl ether, and dried under vacuum at 45° C. to give the desired product (5.57 g, 44%) as a tan-gray solid. A second batch of solids was collected from the filtrate to give the desired product (1.74 g, 14%) as a tan-gray solid. 1H NMR (400 MHz, DMSO-d6) δ 12.20 (br. s., 1H), 8.03 (s, 1H), 3.82 (t, J=7.03, 4H), 3.23 (td, J=11.62, 1.76, 2H), 1.58-1.70 (m, 4H), 1.42-1.55 (m, 1H), 1.10-1.23 (m, 2H); MS (ESI) m/z 327[M+1]+.
the vessel was sealed
The resulting reaction mixture
was stirred vigorously
cooled to room temperature
the resulting mixture heated at 70° C
the vessel was sealed
The resulting reaction mixture
was stirred vigorously
heated at 70° C. for 3 h
cooled to room temperature
the resulting mixture heated at 70° C. for 3.5 h
cooled to room temperature
poured into a separatory funnel
Solids formed while the separatory funnel
was being shaken
The solids were collected by vacuum filtration
washed three times with water
twice with ethyl ether, and dried under vacuum at 45° C.
Source ID: ord-31fc4e5f01be49bdbe1812a52ae3d057