Tetrahydrofuran → HCID 178491273, compound

Temperature

-78 °C

To a mixture of 4-[4-bromo-5-(4H-1,2,4-triazol-3-yl)-2-thienyl]pyridine (222.0 mg, 0.730 mmol) in tetrahydrofuran (5.9 mL, 72.3 mmol) cooled to −78° C. was added dropwise n-BuLi in hexanes (2.50 M, 1.2 mL, 2.90 mmol) under an atmosphere of argon and the mixture was stirred at −78° C. for 30 min. To the solution was added dropwise a solution of 4-methoxybenzaldehyde (0.53 mL, 4.34 mmol) in tetrahydrofuran (5.0 mL, 60 mmol) and the resulting solution was stirred for 30 min at −78° C. The reaction mixture was quenched by the addition of water (2 mL) and the resulting mixture was warmed to room temperature and stirred for 30 min. The mixture was extracted with EtOAc (5 mL) then the organic layer was separated, washed with brine, dried over MgSO4, filtered, and concentrated under the reduced pressure. The obtained residue was purified by prep HPLC to yield 62.0 mg as a yellow solid (23.5%). LCMS: (FA) ES+ , 365. 1H NMR (400 MHz, d6-DMSO) δ: 8.68 (s, 1H), 8.55-8.57 (dd, J=1.5 Hz, 2H), 7.81 (s, br, 1H), 7.63-7.65 (dd, J=1.5 Hz, 2H), 7.40-7.44 (d, J=8.78 Hz, 2H), 6.82-6.84 (d, J=8.78 Hz, 2H), 6.72 (s, br, 1H), 3.68-3.69 (s, br, 3H).

1. stirringthe resulting solution was stirred for 30 min at −78° C
2. customThe reaction mixture was quenched by the addition of water (2 mL)
3. temperaturethe resulting mixture was warmed to room temperature
4. stirringstirred for 30 min
5. extractionThe mixture was extracted with EtOAc (5 mL)
6. customthe organic layer was separated
7. washwashed with brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated under the reduced pressure
11. customThe obtained residue was purified by prep HPLC

ORD record

ord-11a690e99f904827b27522835b16af3d

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796268B2