Dimethylformamide → 6-Methoxy-4-methylpyridine-3-carbaldehyde

HRID 1441481Notes

Reaction equation

HRID 1441481 reaction equation
Br[C:2]1[C:3]([CH3:10])=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[Li]CCCC.CN(C)[CH:18]=[O:19]>O1CCCC1>[CH3:9][O:8][C:5]1[CH:4]=[C:3]([CH3:10])[C:2]([CH:18]=[O:19])=[CH:7][N:6]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 41780025-Bromo-2-methoxy-4-methylpyridineHCID 178418339Butyllithium

Product 1

HCID 144935376-Methoxy-4-methylpyridine-3-carbaldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In Route C, commercially available 5-bromo-2-methoxy-4-methylpyridine in anhydrous tetrahydrofuran is metallated with n-BuLi and then treated with N,N-dimethylformamide to afford 6-methoxy-4-methylnicotinaldehyde. This was converted to the tert-butylimine with tert-butylamine in dichloromethane. Metallation with lithium 2,2,6,6-tetramethylpiperidide (Li-TMP) (cf. J. Org. Chem. 1993, 58, 2463-2467) and addition of N,N-dimethylformamide affords the iminoacetaldehyde which is reduced with sodium cyanoborohydride in methanol to give 2-tert-butyl-6-methoxy-1,2,3,4-tetrahydro-2,7-naphthyridine. Cleavage of the methyl group with refluxing 48% hydrobromic acid and treatment with triflic anhydride in the presence of base gives (VIIb) protected as the tert-butylamine.

Sources & evidence

ORD record
ord-c98d2e199e664b91a139344f76bf8283
Source dataset
uspto-grants-2010_02
Patent number
US07655664B2

Reaction notes

Loading…