3-Carboxybenzaldehyde → 3-Formyl-N-{[4-(trifluoromethoxy)phenyl]methyl}benzamide

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Reaction Steps

to a solution of 300 mg of 3-carboxybenzaldehyde (2 mmoles) and 382 mg of 4-(trifluoromethoxy)benzylamine (2 mmoles) in 5 ml of DCM is successively added 540 mg of 1-hydroxybenzotriazole (HOBt) (4 mmoles) and 0.63 mg of diisopropylcarbodiimide (DIC) (4 mmoles). The reaction mixture is stirred overnight at room temperature and then poured into 20 ml of 10% KH2SO4 solution. The mixture is extracted twice with 15 ml of ethyl acetate. The combined organic extracts are washed with 20 ml of water and 20 ml of brine, dried over MgSO4 and concentrated giving 670 mg of 3-formyl-N-(4-trifluoromethoxy-benzyl)-benzamide (yield=85%). Analytical LC/MS method A: ([M+H]+): 324, RT: 5.24 min (gradient 5 to 85% acetonitrile in 7 min). Compound 60 is prepared as described for example 2 starting with 21.3 mg of of N-Boc-3,5-diketopiperidine (0.1 mmole), 8.3 mg 3-aminopyrazole (0.1 mmole) and 32.3 mg of 3-formyl-N-(4-trifluoromethoxy-benzyl)-benzamide (0.1 mmole) in a mixture of 0.5 ml of ethanol and 0.5 ml of DMF, resulting in 22.5 mg of product 60 after purification by preparative LC/MS. (method A, yield=38%). Analytical LC/MS method A: ([M+H]+): 484, RT: 2.51 min (gradient 2 to 80% acetonitrile in 7 min).

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