(2R)-4-[(9H-Fluoren-9-ylmeth­oxy)carbon­yl]-2-methyl­piperazin-1-ium chloride

The synthesis of the title salt, C20H23N2O2 +·Cl−, was carried out with a precursor of known absolute configuration (R) and the X-ray analysis confirmed that the product retained the absolute configuration. In the crystal, the dominant packing motif is a chain running along [010] generated by N—H⋯Cl hydrogen bonding. C—H⋯O and C—H⋯Cl inter­actions are also observed

Development of Scalable Manufacturing Routes to AZD1981. Application of the Semmler−Wolff Aromatisation for Synthesis of the Indole-4-amide Core

A safe and efficient synthesis of AZD1981 is described in which the indole 4-amide core is formed by a Semmler− Wolff aromatisation of a cyclohexenone oxime fused to a pyrrole ring. The substrate was obtained via Paal−Knorr pyrrole synthesis, followed by incorporation of the key 3-arylthio substituent by reaction with 4-chlorophenylsulfenyl chloride. In this manner, the 1,2,3,4-substitution pattern of the AZD1981 core was regiospecifically established in a concise and efficient telescoped sequence. Accordingly, AZD1981 was obtained in 40% overall yield in six chemical steps, with two isolated crystalline intermediates

Development of Scalable Manufacturing Routes to AZD1981. Application of the Semmler–Wolff Aromatisation for Synthesis of the Indole-4-amide Core

A safe and efficient synthesis of AZD1981 is described in which the indole 4-amide core is formed by a Semmler–Wolff aromatisation of a cyclohexenone oxime fused to a pyrrole ring. The substrate was obtained via Paal–Knorr pyrrole synthesis, followed by incorporation of the key 3-arylthio substituent by reaction with 4-chlorophenylsulfenyl chloride. In this manner, the 1,2,3,4-substitution pattern of the AZD1981 core was regiospecifically established in a concise and efficient telescoped sequence. Accordingly, AZD1981 was obtained in 40% overall yield in six chemical steps, with two isolated crystalline intermediates