Tetrahydrofuran → 6-{[6-(1-oxa-5-azaspiro[2.4]hept-5-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl]methyl}quinoline

Temperature

70 °C

To a flamed dry 3N round bottom flask fitted with a thermometer and condenser was added 95% NaH (69 mg, 2.69 mmol) and anhydrous DMSO (5.0 ml). After stirring for 2 min at R.T. and 70° C. for 45 mins, the reaction mixture was cooled to 3° C. and a solution of trimethylsulfonium iodide (504.1 mg, 2.47 mmol) in DMSO (3.6 ml) was added. After stirring for 30 mins at 3° C., to the reaction mixture, a suspension of 1-[1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl]pyrrolidin-3-one (200 mg, 0.58 mmol) in 1:1 THF: DMSO (16 ml) was added dropwise. After stirring at 0° C. for 3 h, the reaction mixture was poured into an ice cold water (15 ml) and extracted with CH2Cl2 (4×60 ml). The organic layer was washed with brine and dried with MgSO4 and concentrated under reduced pressure. The resulting residue was purified via flash column chromatography eluted with 10% MeOH:CH2Cl2 to give the desired product (130 mg 63%).

1. customTo a flamed dry 3N round bottom flask
2. customfitted with a thermometer and condenser
3. temperaturethe reaction mixture was cooled to 3° C.
4. stirringAfter stirring for 30 mins at 3° C., to the reaction mixture
5. stirringAfter stirring at 0° C. for 3 h
6. extractionextracted with CH2Cl2 (4×60 ml)
7. washThe organic layer was washed with brine
8. dry with materialdried with MgSO4
9. concentrationconcentrated under reduced pressure
10. customThe resulting residue was purified via flash column chromatography
11. washeluted with 10% MeOH

ORD record

ord-836d0cc1d3fe4067a8acb810c8769456

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07732604B2