preparation of 4-(4-methylpiperazine)aniline_industrial additives

background and overview^[1]

4-(4-methylpiperazine)aniline can be used as a pharmaceutical intermediate. it can be prepared by reducing p-fluoronitrobenzene with n-methylpiperazine after nucleophilic substitution. 4-(4-methylpiperazine)aniline can be used to prepare 2-n-aryl-4-n-aryl-5-fluoropyrimidine compounds. this compound has a high fgfr4 inhibitory effect and can be used as an effective potential anticancer drug. fibroblast growth factor receptor (fgfr) is a type of transmembrane receptor tyrosine kinase. currently, the known fgfrs mainly include 4 types, namely fgfr1, fgfr2, fgfr3 and fgfr4. fgfr family members play an important role in controlling cell proliferation and it plays an important role in differentiation signaling pathways.

preparation^[1]

1) synthesis of 4-(4-methylpiperazine)nitrobenzene

dissolve 1.0g (7.1mmol) p-fluoronitrobenzene and 1.42g (14.17mmol) n-methylpiperazine in 10ml dry dimethyl sulfoxide (dmso), and then add to the mixed solution 1.96g (14.17mmol) potassium carbonate. after the reaction was stirred at room temperature for 5 hours, ice water was added to the reaction solution. after precipitation, the mixture was filtered and the filter cake was dried to obtain 1.18g of yellow product with a yield of 75.25%.

2) synthesis of 4-(4-methylpiperazine)aniline

dissolve 1.0g 4-(4-methylpiperazine)nitrobenzene in 10ml methanol, slowly add a catalytic amount of 10% pd/c (mass fraction) while stirring, and pass in hydrogen gas, and react at room temperature for 5 hours. the reaction solution was filtered with suction and the filter cake was washed with methanol. the filtrate was spin-dried under reduced pressure to remove methanol, and the residue was separated by silica gel column chromatography to obtain 0.72g of off-white solid 4-(4-methylpiperazine)aniline, with a yield of 83.7%.

references

[1]cn201910895654.8 a 2-n-aryl-4-n-aryl-5-fluoropyrimidine compound and its preparation method and application