Background and overview[1]
5-Bromo-2,4-dimethylnitrobenzene can be used as a pharmaceutical synthesis intermediate. If 5-bromo-2,4-dimethylnitrobenzene is inhaled, move the patient to fresh air; if skin contact occurs, remove contaminated clothing and rinse the skin thoroughly with soap and water. If discomfort occurs , seek medical attention; if eye contact occurs, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.
Structure
Preparation [1]
5-Bromo-2,4-dimethylnitrobenzene was prepared as follows: fuming nitric acid (32.5ml) was slowly added to 2,6-dimethyl-bromobenzene (10g) cooled in an ice bath. , 54mmol) in a solution of AcOH (75ml). The resulting mixture was warmed to room temperature, stirred for 1 hour, and heated at 80°C for 2 hours. The reaction mixture was cooled to room temperature and poured into ice water with stirring. The resulting precipitate was collected by suction filtration to give the title compound 5-bromo-2,4-dimethylnitrobenzene (10 g), which was used without further purification.
Apply[1]
5-Bromo-2,4-dimethylnitrobenzene can be used as a pharmaceutical synthesis intermediate. If used to prepare 4-bromo-5-methylindole:
Step 1: Preparation of [2-(2-bromo-3-methyl-6-nitro-phenyl)-vinyl]-dimethyl-amine
Heat a mixture of 5-bromo-2,4-dimethylnitrobenzene (12g, 52mmol) and pyrrolidine (2.12ml) in DMF/DMA (180ml) in a sealed tube at 120°C overnight. . The mixture was diluted with water and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated to give the crude title compound (10 g).
Step 2: Preparation of 4-bromo-5-methylindole
Dissolve [2-(2-bromo-3-methyl-6-nitro-phenyl)vinyl]-dimethyl-amine (10g) in AcOH/H2O (100mL:25mL) and cool to 0℃. Treat with Zn (30g), adding slowly in batches. After the addition was complete, the reaction mixture was heated at 110°C overnight. The mixture was diluted with water and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated to give crude product. The crude product was purified by silica gel column chromatography to give the title compound (1.4 g, 20%).
Main reference materials
[1] US20150018367 Aurora and FLT3 kinases modulators
