Sodium Carbonate → 6-(2-chloropyridin-3-yl)-1H-benzimidazole

HRID 2284574Notes

Reaction equation

HRID 2284574 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[NH:13]N=C3)=[CH:6][CH:5]=[CH:4][N:3]=1.Br[C:18]1[CH:19]=[CH:20][C:21]2[N:25]=[CH:24][N:23](C)[C:22]=2[CH:27]=1.[Cl:28][C:29]1[C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][CH:32]=[CH:31][N:30]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[C:7]([C:8]2[CH:16]=[CH:15][C:14]3[N:13]=[CH:22][N:23]([CH3:24])[C:10]=3[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[Cl:28][C:29]1[C:34]([C:18]2[CH:19]=[CH:20][C:21]3[N:25]=[CH:24][NH:23][C:22]=3[CH:27]=2)=[CH:33][CH:32]=[CH:31][N:30]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 120670602-Chloropyridine-3-boronic acid pinacol esterHCID 235376446-Bromo-1-methyl-1H-benzimidazoleHCID 867154695-(2-chloropyridin-3-yl)-1H-indazole

Product 2

HCID 867154816-(2-chloropyridin-3-yl)-1H-benzimidazoleYield 36%HCID 867154826-(2-Chloropyridin-3-yl)-1-methyl-1H-benzimidazole

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

6-(2-Chloropyridin-3-yl)-1-methyl-1H-benzimidazole was synthesized in the similar manner to the preparation of 5-(2-chloropyridin-3-yl)-1H-indazole by heating the mixture of 6-bromo-1-methyl-1H-benzimidazole (1.0 g, 4.7 mmole), 2-chloro-3-pyridine boronic acid pinacol ester (1.4 g, 5.8 mmol), Pd(PPh3)4 (330 mg, 0.28 mmol) and 2M aq.Na2CO3 (7 mL, 14 mmol) in 1,4-dioxane (60 mL). Upon extractive work-up with CH2Cl2 and purification (Combiflash® companion System® with RediSep® silica gel column 24 g, 3% MeOH/EtOAc as a eluting solvent) provided off-white solid of 6-(2-chloropyridin-3-yl)-1H-benzimidazole (430 mg, 36%). 1H NMR (DMSO-d6): δ 8.42 (dd, 1H, J=1.7 and 4.7 Hz), 8.24 (s, 1H), 7.91 (dd, 1H, J=1.7 and 7.6 Hz), 7.60 (d, 1H, J=8.8 Hz), 7.67 (app d, 1H, J=0.7 Hz), 7.53 (dd, 1H, J=J=4.7 and 7.6 Hz), 7.29 (dd, 1H, J=1.7 and 8.8 Hz), 3.86 (s, 3H LCMS: rt 3.85 min (A), purity 94%, MS (m/e) 244 (MH+)

Workup

  1. temperatureby heating
  2. customUpon extractive work-up with CH2Cl2 and purification (Combiflash® companion System® with RediSep® silica gel column 24 g, 3% MeOH/EtOAc as a eluting solvent)

Sources & evidence

ORD record
ord-1c1e3ab9efe84f82a403c50a7b47ae4d
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

Loading…