These common heterocyclic compound, 1996-29-8, name is 1-Bromo-4-chloro-2-fluorobenzene, 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. 1996-29-8
Potassium /-butoxide (3.9 g, 0.33 mmol) was dissolved in DMSO (25 mL). To this solution was added 3 -methyl pyrazole (2.7 g, 0.33 mmol) and the reaction was heated at 50 C for 30 min. l-Bromo-4-chloro-2-fluorobenzene (4.6 g, 0.22 mmol) was then added and the reaction was stirred at 50 C for 16 h. The reaction was cooled to RT and extracted with water and EtOAc, washed with brine, and dried over Na2S04) filtered and concentrated in vacuo. Purification by normal phase silica gel column chromatography (EtO Ac/heptane) provided l-(2- bromo-5-chlorophenyl)-3-methyl-lH-pyrazole and l-(2-bromo-5-chloroplienyl)-5-methyl-lH- pyrazole as a 4: 1 mixture that was used in the next step directly,l-(2-biOmo-5-chlorophenyl)-3-methyl-lH-pyrazole/l-(2-bi mo-5-chlorophenyl)-5- methyl-lH-pyrazole mixture (Intermediate 3, step 1) (1 ,00 g, 3.68 mmol) was dissolved in THF (6 mL) then cooled to 0 C, /-Propyl magnesium chloride (2,76 mL, 2.0 M in THF, 5.52 mmol) was added dropwise and the reaction was warmed to RT for 30 min. The reaction was then cooled to -15 C and paraformaldehyde (166 mg, 5.5 mmol) was added. The reaction mixture was allowed to warm to RT and stirred for 1 h. DMF (500 mL) was added and the reaction was stirred for an additional 1 h. The reaction was quenched with HC1 (2 N, 4 mL), diluted with water, extracted with EtOAc, washed with brine, dried over Na2S04, filtered, and concentrated in vacuo. Purification by normal phase silica gel column chromatography (EtOAc/heptane) provided 4-chloro-2-(3-methyl-pyrazoI-l -yl)-benzaldehyde
Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 1996-29-8.
Reference:
Patent; KAROS PHARMACEUTICALS, INC.; DE LOMBAERT, Stephane; GOLDBERG, Daniel R.; BRAMELD, Kenneth; SJOGREN, Eric Brian; SCRIBNER, Andrew; WO2015/35113; (2015); A1;,
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