Dimethylformamide → tert-butyl 2-[(1R)-1-({[(6R)-6-(5-chloro-2-methoxybenzyl)-3,7-dioxo-4-(2,4,6-trimethoxybenzyl)-1,4-diazepan-1-yl]carbonyl}amino)propyl]isonicotinate

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Reaction Steps

To the compound 5105 described in WO 06-059801A, that is, tert-butyl 2-[(1R)-1-aminopropyl]-isonicotinate D-tartrate (157 mg) in an N,N-dimethylformamide (1.5 ml) solution, triethylamine (0.113 ml) was added under ice cooling, and the mixture was stirred at that temperature for 5 minutes. To the reaction solution, the compound S141C described in WO 06-059801A, that is, (6R)-2-chlorophenyl 6-(5-chloro-2-methoxybenzyl)-3,7-dioxo-4-(2,4,6-trimethoxybenzyl)-1,4-diazepane-1-carboxylate (250 mg) and 4-dimethylaminopyridine (49 mg) were added, and the mixture was stirred at 0° C. for 18 hours. The reaction solution was diluted with ethyl acetate, then was successively washed with saturated aqueous ammonium chloride solution and brine. The organic layer was dried over anhydrous sodium sulfate, then was concentrated. The residue was purified by flash column chromatography (silica gel, hexane/ethyl acetate=1/1 to 1/2) to obtain tert-butyl 2-[(1R)-1-({[(6R)-6-(5-chloro-2-methoxybenzyl)-3,7-dioxo-4-(2,4,6-trimethoxybenzyl)-1,4-diazepan-1-yl]carbonyl}amino)propyl]isonicotinate (compound S39a) (210 mg).

Provenance & Evidence