Cl.[O:2]1[C:6]2[CH2:7][NH:8][CH2:9][CH2:10][C:5]=2[CH:4]=[CH:3]1.[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([OH:25])=O)=[CH:14][CH:13]=1.[CH2:26]([N:28]([CH2:31]C)[CH2:29]C)C.C(P(=O)(OCC)OCC)#N.CNC.C=O>ClCCl>[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([N:8]2[CH2:9][CH2:10][C:5]3[CH:4]=[C:3]([CH2:26][N:28]([CH3:31])[CH3:29])[O:2][C:6]=3[CH2:7]2)=[O:25])=[CH:14][CH:13]=1To a solution of 0.319 g (2.000 mmol) of 4,5,6,7-tetrahydrofuro[2,3-c]pyridine hydrochloride, 0.498 g (2.2 mmol) of 6-(4-chlorophenyl)hexanoic acid and 1.1 ml (8.0 mmol) of triethylamine in 30 ml of dichloromethane, 0.489 g (3.0 mmol) of diethyl cyanophosphonate was added dropwise under ice-cooling, followed by overnight stirring at room temperature. After the solvent was distilled off, water was added, followed by 2 extractions with ethyl acetate. The combined organic layer was washed with water and dried over anhydrous sodium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was dissolved in 10 ml of acetic acid; 0.270 ml (3.00 mmol) of 50% aqueous dimethylamine and 0.245 ml (3.00 mmol) of 37% aqueous formaldehyde were added, followed by stirring at 100° C. for 90 minutes. After the solvent was distilled off under reduced pressure, the residual solution was alkalified with 5% aqueous sodium hydrogen carbonate and extracted with ethyl acetate 2 times. The combined organic layer was washed with water and dried over anhydrous sodium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (ethyl acetate/methanol=5/1) to yield the desired product.
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