反应详情

Ethyl 3-[(4-fluorobenzoyl)amino]-6,6-dimethyl-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate hydrochloride (0.5 g, 1.3 mmol), in dichloromethane (25 ml), was treated with N,N-diisopropylethylamine (1.13 ml, 6.5 mmol, 5 eq) and TBTU (0.542 g, 1.69 mmol, 1.3 eq), at room temperature for 1 hour, and then 1-methyl-piperidine-4-carboxylic acid hydrochloride (0.29 g, 1.61 mmol, 1.2 eq) was added. The reaction was stirred overnight (TLC: CH2Cl2/MeOH 90/10). The solution was washed with saturated sodium hydrogencarbonate aqueous solution and brine, the organic phase was dried over sodium sulfate and concentrated. The residue was dissolved in methanol (16 ml), treated with TEA (2 ml, 14.3 mmol, 11 eq) and stirred overnight at room temperature. (TLC: CH2Cl2/MeOH/NH4OH 90/10/1). After evaporation, the solid was purified by flash chromatography (eluent: CH2Cl2/MeOH/NH4OH 90/10/2). The solid was treated with diisopropylether and filtered to afford 0.36 g of the title compound in 69% yield.

1. washThe solution was washed with saturated sodium hydrogencarbonate aqueous solution and brine
2. dry with materialthe organic phase was dried over sodium sulfate
3. concentrationconcentrated
4. dissolutionThe residue was dissolved in methanol (16 ml)
5. customAfter evaporation
6. customthe solid was purified by flash chromatography (eluent: CH2Cl2/MeOH/NH4OH 90/10/2)
7. additionThe solid was treated with diisopropylether
8. filtrationfiltered