反应详情

5′-(3-Furoylamino)-2′-methyl-1,1′-biphenyl-4-carboxylic acid (50 mg, 0.156 mmol), 1-t-butyloxycarbonyl-4-aminomethylpiperidine (33.3 mg, 0.156 mmol), HATU (59.2 mg, 0.156 mmol), HOBT (21 mg, 0.156 mmol) and DIPEA (27 μl, 0.156 mmol) in DMF (2 ml) were stirred at room temperature for 18 h. The reaction was diluted with ethyl acetate (150 ml), washed with water (2×30 ml) and dried (magnesium sulphate). The solvent was evaporated under vacuum and the residue chromatographed on a silica flash column eluting with DCM/methanol/triethylamine (96:2:2). Concentration of the product fractions under vacuum N-[4′-({[(1-t-butyloxycarbonylpiperidin-4-yl)methyl]amino}carbonyl)-6-methyl-1,1′-biphenyl-3-yl]-3-furamide (45 mg, 56%). NMR; δH [2H6]-DMSO 9.91,(1H, s), 8.56,(1H, t), 8.35,(1H, s), 7.91,(2H, d), 7.78,(1H, t), 7.66,(1H, dd), 7.59,(1H, d), 7.43,(2H, d), 7.27,(1H, d), 6.98,(1H, m), 3.93,(2H, m), 3.17,(2H, t), 2.68,(2H, b), 2.19,(3H, s), 1.74,(1H, b), 1.67,(2H, m), 1.38,(9H, s), 1.03,(2H, m). LCMS: retention time 3.50 min, [MH-BOC]+418.

1. washwashed with water (2×30 ml)
2. dry with materialdried (magnesium sulphate)
3. customThe solvent was evaporated under vacuum
4. customthe residue chromatographed on a silica flash column
5. washeluting with DCM/methanol/triethylamine (96:2:2)