2-Aminopyridine → 5-Methyl-8-(pyridinylamino)-6-trifluoromethyl-1,3,4,4a,5,9b-hexahydro-pyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

8-bromo-5-methyl-6-trifluoromethyl-1,3,4,4a,5,9b-hexahydro-pyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester (Example 44 or 45, 1.0 eq.), aminopyridine (3.0 eq.), and NaOt-Bu (3.0 eq.) were dissolved in anhydrous toluene (0.17 M). The mixture was degassed with argon for 30 min. Pd2(dba)3 (0.06 eq.) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.18 eq.) were added; the reaction was heated at 80° C. for 16 h. The reaction was cooled to room temperature, diluted with EtOAc, filtered through a bilayer pad of diatomaceous earth and silica gel, and concentrated. Purification of the residue by flash column chromatography (silica gel, 2–30% EtOAc/hexanes) provided 5-methyl-8-(pyridinylamino)-6-trifluoromethyl-1,3,4,4a,5,9b-hexahydro-pyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester derivatives. The intermediate was dissolved in CH2Cl2/TFA (5/1) at rt stirred for 1 h. Upon concentration in vacuo, the residue was partitioned between CH2Cl2/1 M NaOH. The aqueous phase was extracted with CH2Cl2. The combined organic phases were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography to give the title compound.

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