Hydrogen Bromide → 1,2,3,4-Tetrahydro-2,7-naphthyridine

HRID 643487Notes

Reaction equation

HRID 643487 reaction equation
Br.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.C([N:21]1[CH2:30][CH2:29][C:28]2[C:23](=[CH:24][N:25]=[C:26](OC)[CH:27]=2)[CH2:22]1)(C)(C)C>>[CH2:24]1[C:23]2[C:28](=[CH:29][CH:30]=[N:21][CH:22]=2)[CH2:27][CH2:26][NH:25]1

Participants

4

Reactant 3

HCID 260Hydrogen BromideHCID 67749Trifluoromethanesulfonic anhydrideHCID 442276722-(1,1-Dimethylethyl)-1,2,3,4-tetrahydro-6-methoxy-2,7-naphthyridine

Product 1

HCID 178014131,2,3,4-Tetrahydro-2,7-naphthyridine

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.

Workup

  1. customgives (VIIb)

Sources & evidence

ORD record
ord-f44eb40c1a1843af9dea1b9e0420cff8
Source dataset
uspto-grants-2010_04
Patent number
US07700604B2

Reaction notes

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