1-Methyl-1H-1,2,3-triazole-5-carbaldehyde → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

Temperature

-70 °C

To a 50 mL flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (1.45 g, 3.37 mmol, Intermediate 47: step d) was added THF (25 mL) at room temp which resulted in a colorless homogeneous mixture. The solution was cooled to −70° C. which remained homogeneous and then n-BuLi (2.5 M in hexanes, 1.3 mL, 3.25 mmol) was added dropwise. The color of the solution became a dark reddish-brown color. After 2 minutes, 1-methyl-1H-1,2,3-triazole-5-carbaldehyde (580 mg, 5.22 mmol, in 3 mL THF, Intermediate 50: step a) was introduced and the color of the mixture went from dark brown to greenish to a yellow color within about 2 minutes. The mixture was allowed to warm to −20° C. over 45 minutes at which time the contents were quenched with aqueous NH4Cl. The mixture was diluted further with water and extracted with EtOAc (5×40 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to give a yellowish oil. The crude material was chromatographed on silica gel (5% CH3CN-DCM increasing to 30% CH3CN+2% MeOH) to give the title compound as an off white foam.

1. customresulted in a colorless homogeneous mixture
2. customwithin about 2 minutes
3. temperatureto warm to −20° C. over 45 minutes at which time the contents
4. customwere quenched with aqueous NH4Cl
5. additionThe mixture was diluted further with water
6. extractionextracted with EtOAc (5×40 mL)
7. washThe combined organics were washed with brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customto give a yellowish oil
12. customThe crude material was chromatographed on silica gel (5% CH3CN-DCM increasing to 30% CH3CN+2% MeOH)

ORD record

ord-67f24532261640f0ad78f30a1f6f6d14

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09290476B2