These common heterocyclic compound, 2644-93-1, name is 1,3,5-Trimethyl-1H-pyrazole-4-carbaldehyde, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. category: pyrazoles-derivatives
To a flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (1.37 g, 3.86 mmol, Intermediate 10: step d) was added THF (45 mL) at room temperature which resulted in a colorless homogeneous mixture. The solution was cooled to -78 C. and then n-BuLi (2.5 M in hexanes, 1.8 mL, 4.5 mmol) was added dropwise. The color of the solution became a reddish-brown color. After 4 minutes, 1,3,5-trimethyl-1H-pyrazole-4-carbaldehyde (300 mg, 2.17 mmol, in 3 mL THF) was introduced and the color of the mixture changed from reddish-brown to a yellow-greenish color over 5 minutes. The mixture was allowed to warm to 0 C. over 45 minutes at which time the reaction was quenched with aqueous NH4Cl solution. The mixture was diluted further with water and extracted with EtOAc (3*150 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to give a light orange foam. FCC on silica gel (2% MeOH-DCM increasing to 8% MeOH-DCM) afforded the title compound as a light yellow amorphous solid. 1H NMR (500 MHz, CDCl3) delta ppm 8.23 (s, 1H), 7.78 (d, J=8.6 Hz, 1H), 7.56-7.47 (m, 3H), 7.40 (d, J=8.1 Hz, 2H), 6.01 (d, J=3.0 Hz, 1H), 4.35 (s, 2H), 4.06 (s, 3H), 3.70 (s, 3H), 2.14 (s, 3H), 2.12 (s, 3H), 2.09 (d, J=3.3 Hz, 1H). MS (ESI): mass calcd. for C25H23ClF3N3O2, 489.1; m/z found, 490.1 [M+H]+.
The synthetic route of 1,3,5-Trimethyl-1H-pyrazole-4-carbaldehyde has been constantly updated, and we look forward to future research findings.
Reference:
Patent; JANSSEN PHARMACEUTICA NV; LEONARD, KRISTI A.; BARBAY, KENT; EDWARDS, JAMES P.; KREUTTER, KEVIN D.; KUMMER, DAVID A.; MAHAROOF, UMAR; NISHIMURA, RACHEL; URBANSKI, MAUD; VENKATESAN, HARIHARAN; WANG, AIHUA; WOLIN, RONALD L.; WOODS, CRAIG R.; FOURIE, ANNE; XUE, XIAOHUA; CUMMINGS, MAXWELL D.; US2015/105372; (2015); A1;,
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