1,1'-Biphenyl, mixt. with 1,1'-oxybis(benzene) → 1,5-Naphthyridine
Reaction equation
CO[C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][N:4]=1.C(OCC)(OCC)OCC.[CH:20]1[CH:25]=CC(C2C=CC=CC=2)=C[CH:21]=1.C1C=CC(OC2C=CC=CC=2)=CC=1>>[N:4]1[C:5]2[C:6](=[N:9][CH:21]=[CH:20][CH:25]=2)[CH:7]=[CH:8][CH:3]=1Participants
4
Procedure
An alternative synthetic sequence to obtain the key intermediate E is described in Scheme 2. Commercially available 2-methoxy-5-aminopyridine F is converted by heating in the presence of ester B and triethyl orthoformate to the condensation product G as a mixture of olefin isomers (Scheme 2). Intermediate G is added to hot Dowtherm™ A to facilitate the ring closure and to yield the 1,5-naphthyridine H. Demethylation at the 6-position of H is conducted by treatment with trimethylsilyl chloride and sodium iodide in refluxing acetonitrile to give intermediate I, which may be used, without purification, for the reaction with phosphorus oxychloride to provide the key intermediate E (Scheme 2).
Sources & evidence
- ORD record
- ord-da1082d22aac4f64a7983d4d31998800
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09067937B2
Reaction notes
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