Benzyl Bromide → 2-(Benzyloxy)pyridine

HRID 278927Notes

Reaction equation

HRID 278927 reaction equation
Cl[C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[CH:3]=1.[CH2:9](Br)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C1C=CC=CC=1>[CH2:9]([O:8][C:4]1[CH:3]=[CH:2][CH:7]=[CH:6][N:5]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

4

Reactant 2

HCID 7498Benzyl BromideHCID 27576114-Chloropyridin-2-ol

Product 1

HCID 2958592-(Benzyloxy)pyridine

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

Reaction of 4-chloropyridone (XXXXII) with an aryl halide, such as benzyl bromide in benzene and in the presence of Ag2CO3 as described in Scheme 13 (Smith A. M.; et al. J. Med. Chem. 36, 8, 1993) and at temperature ranges of 30-80° C. afforded the corresponding 2-benzyloxypyridine (XXXXVII). This was coupled with an arylboronic acid, ArB(OH)2 under palladium-catalyzed conditions to give (XXXXIX). The benzyloxy group can be removed by treatment with a strong acid, such as trifluoroacetic, triflic, sulfuric, HCl, etc. to give pyridone (L). This was converted to the 2-halopyridine with the action of POX3, PX5 or the corresponding triflate, tosylate or mesylate, which was displaced with a primary amine RNH2 to give (LI). The nitro group was reduced under conditions described in scheme 13 and the aminopyridine was cyclized to the imidazolo[4,5-b]pyridine (LII) under conditions described in scheme 13.

Workup

  1. customas described in Scheme 13 (Smith A. M.; et al. J. Med. Chem. 36, 8, 1993) and at temperature ranges of 30-80° C.

Sources & evidence

ORD record
ord-cd25212ea30241448fbe360c8b5bed6a
Source dataset
uspto-grants-2002_03
Patent number
US06362180B1

Reaction notes

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