2,4,6-Trichlorobenzoyl chloride → N-(3-cyclopropyl-1-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-1H-indazol-4-yl)-7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

To lithium 7-(2-(4-methylpiperazin-1-yl)ethoxy)imidazo[1,2-a]pyridine-3-carboxylate (Example 56, Step A; 70.5 mg, 0.23 mmol) was added N-Methylpyrrolidinone (1 mL). The suspension was heated in order to affect dissolution. The reaction mixture was cooled in an ice-water bath under nitrogen, and 2,4,6-trichlorobenzoyl chloride (35.5 μL, 0.23 mmol) was added dropwise. The cold bath was removed once the addition was complete and the reaction mixture was stirred for a further 1 hour. The reaction mixture became cloudy. A solution of 3-cyclopropyl-1-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-1H-indazol-4-amine (48 mg, 0.168 mmol) in anhydrous N-Methylpyrrolidinone (1 mL) was then added to the reaction mixture, and the mixture was heated to 88° C. for 13.5 hours. The reaction mixture was cooled, diluted with water, and extracted multiple times with dichloromethane. The combined dichloromethane extracts were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude residue was purified by preparative thin-layer chromatography (silica, eluting with 7N ammonia/MeOH:MeOH:DCM in a 3:7:90 ratio) to afford the product (51.6 mg) as a dark yellow solid. MS (ES+APCI) m/z=572 (M+H).

Provenance & Evidence