反応式
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[CH3:9][O:10][C:11]1[CH:30]=[CH:29][C:14]([O:15]C2C=C(N3CC4CC3CN4)C=NC=2)=[CH:13][CH:12]=1.COC1C=CC([O-])=CC=1.[Na+]>CN(C)C=O>[Br:8][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([O:15][C:14]2[CH:29]=[CH:30][C:11]([O:10][CH3:9])=[CH:12][CH:13]=2)[CH:7]=1参加物
実験手順
In an alternative approach to the synthesis of pyridine-substituted pyridyl diazabicyclic compounds, 3,5-dibromopyridine can be converted into the corresponding 3-bromo-5-alkoxy- and 3-bromo-5-aryloxypyridines by the action of sodium alkoxides or sodium aryloxides. Procedures such as those described by Comins et al., J. Org. Chem. 55: 69 (1990) and Hertog et al., Recueil Trav. Chim. Pays-Bas 74: 1171 (1955) are used. This is exemplified by the preparation 2-(5-(4-methoxyphenoxy)-3-pyridyl)-2,5-diazabicyclo[2.2.1]heptane. Reaction of 3,5-dibromopyridine with sodium 4-methoxyphenoxide in N,N-dimethylformamide gives 3-bromo-5-(4-methoxyphenoxy)pyridine. Coupling of 3-bromo-5-(4-methoxyphenoxy)pyridine with (1S,4S)-N-(tert-butoxycarbonyl)-2,5-diazbicyclo[2.2.1]heptane in the presence of sodium tert-butoxide and a catalytic amount of tris(dibenzylideneacetone)dipalladium(0) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl in toluene provides (1S,4S)-2-(5-(4-methoxyphenoxy)-3-pyridyl)-5-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]heptane. Removal of the N-tert-butoxycarbonyl group, using trifluoroacetic acid, produces (1S,4S)-2-(5-(4-methoxyphenoxy)-3-pyridyl)-2,5-diazabicyclo[2.2.1]heptane.
出典と根拠
- ORDレコード
- ord-f5aa14df5a4f456685a1786b8ec8fd16
- 出典データセット
- uspto-grants-2005_02
- 特許番号
- US06852721B2
関連ノート
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