Processes for the manufacture of propane-1-sulfonic acid (3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl)-amide

摘要

According to the present invention there are provided novel processes for the manufacture of the compound of formula 1;
as well as intermediates and novel synthesis routes for key intermediates used in those processes.

主权项

1. A process for the manufacture of a compound of formula 1,comprisinga) reacting a compound of formula 2in the presence of a palladium catalyst, a base, and a compound of formula 3in a Suzuki-Miyaura reaction to give a compound of formula 4b) reacting the compound of formula 4 in the presence of a halogenation reagent to give a compound of formula 5wherein X is I (5a) or Br (5b); andc) reacting the compound of formula 5
c-1) with a compound of formula (D); or c-2) with a compound of formula 7 in a Sonogashira reaction and then with a strong base;to give a compound of formula 8d) reacting the compound of formula 8 in the presence of a compound of formula 9 and under conditions of a Friedel-Crafts Acylationto give the compound of formula 1, whereinR1, R2, R3, and R4 are all methyl, or together with the carbon atoms to which they are attached form a phenyl ring; andR5 is —(C1-C6)alkyl or benzyl.