Process for large-scale production of 1 - [(2-bromophenyl) sulfonyl] -5-methoxy-3 - [(4-methyl-1-piperazinyl) methyl] -1H-indole monohydrate dimesylate
A suitable process for the large-scale production of 1 - [(2-bromophenyl) sulfonyl] -5-methoxy-3 - [(4-methyl-1-piperazinyl) methyl] -1H-indole monohydrate dyesylate of the formula ( I), comprising: ** (See formula) ** Step (i): React 1-methylpiperazine of formula 1 ** (See formula) ** in the presence of acetic acid and aqueous formaldehyde of formula 2 a a temperature in the range of 15 ° C to 35 ° C for a period of 1.5 hours to 2.5 hours to obtain the Mannich adduct； ** (See formula) ** Step (ii): React the Mannich adduct with 5-methoxyindole of formula 3 ** (See formula) ** in the presence in methanol at a temperature in the range of 15 ° C at 40 ° C for a period of 2.5 hours to 3.5 hours to obtain 5-methoxy-3 - [(4-methyl-1-piperazinyl) methyl] -1H-indole of formula 4； ** (See formula) ** Step (iii): Crystallize 5-methoxy-3 - [(4-methyl-1-piperazinyl) methyl] -1H-indole of formula 4 in toluene by heating the solution to 85 ° C - 95 ° C for a period of 1 hour, followed by cooling the solution to 10 ° C - 15 ° C for the period of 3 hours； Step (iv): recrystallize 5-methoxy-3 - [(4-methyl-1-piperazinyl) methyl] -1H-indole of formula 4 in toluene by heating the solution at 95 ° C - 105 ° C for a period of 2 hours, followed by cooling the solution to 10 ° C -15 ° C for a period of 3 hours； Step (v): react the crystalline 5-methoxy-3 - [(4-methyl-1-piperazinyl) methyl] -1H-indole obtained from formula 4 with 2-bromobenzenesulfonyl chloride of formula 5； ** (See formula) ** in the presence of tetrahydrofuran and potassium hydroxide at a temperature in the range of 20 ° C to 40 ° C for a period of 3.5 hours to 4.5 hours to obtain 1 - [(2-bromophenyl) sulfonyl] -5-methoxy-3 - [(4-methyl-1-piperazinyl) methyl] -1Hindole of the formula 6； ** (See formula) ** Step (vi): convert 1 - [(2-bromophenyl) sulfonyl] -5-methoxy-3 - [(4-methyl-1-piperazinyl) methyl] -1H-indole of the formula 6 in the presence of ethanol and metasulfonic acid at a temperature in the range of 15 ° C to
