Methanol → 6-Benzyl-2-methoxy-5,6,7,8-tetrahydro-[1,6]naphthyridine

Reaction equation

[Na].[CH3:2][OH:3].[CH2:4]([N:11]1[CH2:20][CH2:19][C:18]2[N:17]=[C:16](Cl)[CH:15]=[CH:14][C:13]=2[CH2:12]1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>CN(C)C=O>[CH2:4]([N:11]1[CH2:20][CH2:19][C:18]2[N:17]=[C:16]([O:3][CH3:2])[CH:15]=[CH:14][C:13]=2[CH2:12]1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

Procedure

Sodium (2.49 g, 0.11 mol) was added portionwise to methanol (70 ml) and was stirred at room temperature under a nitrogen atmosphere for 30 minutes. N,N-dimethylformamide (35 ml) was added and the solution was added to 6-benzyl-2-chloro-5,6,7,8-tetrahydro-[1,6]naphthyridine (2.8 g, 10.9 mmol) (see reference WO98/30560 Example 33b). The mixture was heated at reflux under a nitrogen atmosphere for 5 days and then was evaporated under reduced pressure. The residue was purified by chromatography on silica gel using methanol in dichloromethane (gradient from 0:100 to 4:96) and the material obtained was dried under vacuum to give the title compound (2.54 g).