Ethanol → [8-(4-Fluoro-phenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[1-(3-methyl-[1,2,4]thiadiazol-5-yl)-piperidin-4-yl]-amine

Temperature

85 °C

To a solution of 8-(4-fluoro-phenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (60 mg, 0.258 mmol) and 1-(3-methyl-[1,2,4]thiadiazol-5-yl)-piperidin-4-one (76 mg, 0.387 mmol) in dry dichloroethane (3 mL) was added tetraisopropyl-orthotitanate (236 μL, 0.775 mmol) under an argon atmosphere and heated to 85° C. for 12 hours. The reaction mixture was cooled to room temperature, sodium borohydride (20 mg, 0.517 mmol) and ethanol (1.5 mL) were added and stirred at room temperature for 3 hour and at 50° C. for 30 minutes. The reaction mixture was cooled to room temperature and evaporated. An aqueous solution of Na2CO3 (2M) was added to the residue. The aqueous phase was extracted with ethyl acetate, the combined organic phases were dried over sodium sulfate, the solvent was evaporated and the residue purified by silica gel chromatography using dichloromethane/methanol (with 10% ammonia) as eluent. The title compound was obtained as a white solid (28.8 mg, 27%).

1. temperatureThe reaction mixture was cooled to room temperature
2. temperatureThe reaction mixture was cooled to room temperature
3. customevaporated
4. additionAn aqueous solution of Na2CO3 (2M) was added to the residue
5. extractionThe aqueous phase was extracted with ethyl acetate
6. dry with materialthe combined organic phases were dried over sodium sulfate
7. customthe solvent was evaporated
8. customthe residue purified by silica gel chromatography

ORD record

ord-4ac1881fe938421b9ae37be053094ad4

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08486967B2