[CH2:1]([N:8]1[CH2:12][CH2:11][C@@H:10]([NH:13][C:14]2[C:24]([F:25])=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:16](Cl)[N:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])=O.[NH4+]>C(O)C.[Pd]>[CH2:1]([N:8]1[CH2:12][CH2:11][C@@H:10]([NH:13][C:14]2[C:24]([F:25])=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][N:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1To a solution of ethyl 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-2-chloro-5-fluoronicotinate (500 mg) in ethanol (20 mL) were added ammonium formate (584 mg) and 10% Pd/C (300 mg) at 25° C. and the mixture was heated to reflux with stirring for 1 hour. After cooling, the catalyst in the reaction mixture was removed by filtration. The filtrate was evaporated in vacuo. To the residue were added CH2Cl2(30 ml), ethanol (7 mL), and benzaldehyde (140 mg) at 25° C. After stirring for 5 minutes, sodium triacetoxyborohydride (280 mg) was 3 hours, and then poured into a mixture of CH2Cl2 and aqueous NaHCO3. The organic layer was separated, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (11 g) using a mixed solvent of dichloromethane and MeOH (100:1 to 40:1). The fractions containing the objective compound were collected and evaporated under reduced pressure. Title compound (302 mg, 66%) was obtained as colorless syrup.
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