Pyridine → 3-(Azetidin-1-YL)-8-chloroimidazo[1,5-A]pyrazine

To a stirred solution of N-((3-chloropyrazin-2-yl)methyl)azetidine-1-carboxamide (41.9 mmol, 9.5 g) in acetonitrile (130 mL) were added N,N-dimethylformamide (7.12 mmol, 0.55 mL), pyridine (419 mmol, 33.8 mL) and finally phosphorous oxychloride (210 mmol, 19.5 mL). After 7 minutes the reaction mixture was quenched by adding it to a cooled (0° C.) mixture of anhydrous 7N ammonia in methanol (150 mL) and acetonitrile (200 mL) and subsequently concentrated in vacuo. The residue was dissolved in dichloromethane, water (150 mL) and saturated aqueous sodium hydrogencarbonate (150 mL) were added and this mixture extracted six times with dichloromethane (100 mL). The combined organic extracts were dried (sodium sulfate) and concentrated in vacuo. Purification by column chromatography (silica gel; dichloromethane/methanol) gave 4.5 g of the title compound.

1. customAfter 7 minutes the reaction mixture was quenched
2. additionby adding it to
3. temperaturea cooled
4. addition(0° C.) mixture of anhydrous 7N ammonia in methanol (150 mL) and acetonitrile (200 mL)
5. concentrationsubsequently concentrated in vacuo
6. dissolutionThe residue was dissolved in dichloromethane
7. additionwater (150 mL) and saturated aqueous sodium hydrogencarbonate (150 mL) were added
8. extractionthis mixture extracted six times with dichloromethane (100 mL)
9. dry with materialThe combined organic extracts were dried (sodium sulfate)
10. concentrationconcentrated in vacuo
11. customPurification by column chromatography (silica gel; dichloromethane/methanol)

ORD record

ord-db460795a1634665a5e319fc6d92e101

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658794B2