Sodium Carbonate → 5-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)nicotinaldehyde

HRID 391309Notes

Reaction equation

HRID 391309 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8](I)[N:7]([CH3:11])[C:6]=2[CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:27]2[CH:28]=[N:29][CH:30]=[C:31]([CH:34]=2)[CH:32]=[O:33])O1>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.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C:27]3[CH:28]=[N:29][CH:30]=[C:31]([CH:34]=3)[CH:32]=[O:33])[N:7]([CH3:11])[C:6]=2[CH:12]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 49926405-(Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-carbaldehydeHCID 595784096-chloro-2-iodo-1-methyl-1H-benzo[d]imidazole

Product 1

HCID 595784235-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)nicotinaldehyde

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

A flask was charged with 6-chloro-2-iodo-1-methyl-1H-benzo[d]imidazole (627 mg, 2.145 mmol), DMF (10 mL), 2M aqueous sodium carbonate (2.145 mL, 4.29 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinaldehyde (1 g, 4.29 mmol). Nitrogen was bubbled through the mixture for 10 min and polymer bound Pd(PPh3)4 (1.19 g, 0.107 mmol) was added. The mixture was heated to 160° C. under micro-wave irradiation for 30 min. The mixture was filtered through a thin pad of celite, which was washed with EtOAc (100 mL). The filtrate was poured into water (200 mL) and extracted with EtOAc (500 mL). The organic phase was washed with water (50 mL), dried over Na2SO4 and concentrated. The residue was purified by silica chromatography eluting with 20 to 100% EtOAc in heptane to give 5-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)nicotinaldehyde. ESI-MS: m/z 272.1 (M+H)+.

Workup

  1. customNitrogen was bubbled through the mixture for 10 min
  2. filtrationThe mixture was filtered through a thin pad of celite, which
  3. washwas washed with EtOAc (100 mL)
  4. additionThe filtrate was poured into water (200 mL)
  5. extractionextracted with EtOAc (500 mL)
  6. washThe organic phase was washed with water (50 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe residue was purified by silica chromatography
  10. washeluting with 20 to 100% EtOAc in heptane

Sources & evidence

ORD record
ord-75f5077e3bc1422db8225dbe6eb2897c
Source dataset
uspto-grants-2013_02
Patent number
US08383827B2

Reaction notes

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