Ammonium Hydroxide → 3-Methoxy-2,7-naphthyridine

HRID 643485Notes

Reaction equation

HRID 643485 reaction equation
C[Si](C#C)(C)C.[CH3:7][O:8][C:9]1[CH:16]=[C:15]([C:17]#[C:18][Si](C)(C)C)[C:12]([CH:13]=O)=[CH:11][N:10]=1.[OH-].[NH4+:24]>C(O)C>[CH3:7][O:8][C:9]1[N:10]=[CH:11][C:12]2[C:15]([CH:16]=1)=[CH:17][CH:18]=[N:24][CH:13]=2

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 66111TrimethylsilylacetyleneHCID 59164393HCID 59164393, compound

Product 1

HCID 591643983-Methoxy-2,7-naphthyridine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Preferably the 1,2,3,4-tetrahydro-2,7-naphthyridine intermediate (VIIb) can be synthesised as shown in Schemes 3 and 4. In Route B, commercially available 6-methoxynicotinaldehyde is treated successively with the lithium salt of N,N,N′-trimethylethylenediamine, then n-BuLi in hexanes and finally iodine to afford the 4-iodo-6-methoxynicotinaldehyde (cf. Tetrahedron Lett. 1993, 34(39), 6173-6176). The iodo compound is coupled with trimethylsilylacetylene under usual Sonagashira-Hagihara conditions (Synthesis 1980, 627-630) and the resulting 6-methoxy-4-[(trimethylsilyl)ethynyl]nicotinaldehyde is condensed with ammonium hydroxide in ethanol to give 3-methoxy-2,7-naphthyridine (Synthesis 1999, 2, 306-311). Regioselective catalytical reduction (cf. Eur. J. Med. Chem. Ther. 1996, 31(11), 875-888) affords 6-methoxy-1,2,3,4-tetrahydro-2,7-naphthyridine. Demethylation and N-protection with BOC-anhydride and finally treatment of the resulting tert-butyl 6-hydroxy-3,4-dihydro-2,7-naphthyridine-2(1H)-carboxylate with triflic anhydride in a two-phase system gives (VIIb).

Sources & evidence

ORD record
ord-2e7a6d2ad0b94ecba92232e3d44ca7fa
Source dataset
uspto-grants-2010_04
Patent number
US07700604B2

Reaction notes

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