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

HRID 2284573Notes

Reaction equation

HRID 2284573 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.BrC1[C:19](Cl)=[N:20]C=CC=1.N1C2C=CC(B3OC(C)(C)C(C)(C)O3)=CC=2N=C1.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:19][NH:20][C:10]=3[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 6933243-Bromo-2-chloropyridineHCID 867154695-(2-chloropyridin-3-yl)-1H-indazoleHCID 178431023HCID 178431023, compound

Product 1

HCID 867154816-(2-chloropyridin-3-yl)-1H-benzimidazoleYield 26%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

6-(2-Chloropyridin-3-yl)-1H-benzimidazole was synthesized in the similar manner to the preparation of 5-(2-chloropyridin-3-yl)-1H-indazole by heating the mixture of 3-bromo-2-chloropyridine (0.70 g, 3.63 mmol), 1H-benzimidazole-5-boronic acid pinacol ester (0.8 g, 3.27 mmole), Pd(PPh3)4 (330 mg, 0.28 mmol) and 2M aq.Na2CO3 (4 mL, 8 mmol) in 1,4-dioxane (30 mL). Upon extractive work-up with CH2Cl2 and purification of the concentrate by flash silica gel column chromatography (Combiflash® companion System® with RediSep® silica gel column 24 g, 3% MeOH/EtOAc as a eluting solvent upon dry loading the concentrate absorbed on silica gel) provided 6-(2-chloropyridin-3-yl)-1H-benzimidazole (200 mg, 26%). 1H NMR (DMSO-d6): δ 12.57 (s, 1H), 8.95 (dd, 1H, J=1.7 and 4.9 Hz), 8.28 (s, 1H), 7.90 (dd, 1H, J=1.7 and 7.6 Hz), 7.70-7.62 (m, 2H), 7.58 (dd, 1H, J=4.9 and 7.6 Hz), 7.29-7.27 (app s, 1H).LCMS: rt 3.71 min (A), purity 96%, MS (m/e) 230 (MH+).

Workup

  1. temperatureby heating
  2. customUpon extractive work-up with CH2Cl2 and purification of the
  3. concentrationconcentrate by flash silica gel column chromatography (Combiflash® companion System® with RediSep® silica gel column 24 g, 3% MeOH/EtOAc as a eluting solvent
  4. customupon dry loading the concentrate
  5. customabsorbed on silica gel)

Sources & evidence

ORD record
ord-792ba35e8fa44d8c8675b2a6499529d2
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

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