Sodium Dithionite → 5-Bromo-2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-7-(trifluoromethoxy)-1H-benzo[d]imidazole

HRID 2275032Notes

Reaction equation

HRID 2275032 reaction equation
[Br:1][C:2]1[CH:9]=[C:8]([O:10][C:11]([F:14])([F:13])[F:12])[C:5]([NH:6][CH3:7])=[C:4]([N+:15]([O-])=O)[CH:3]=1.[CH2:18]([N:20]1[C:24]2=[N:25][CH:26]=[CH:27][CH:28]=[C:23]2[CH:22]=[C:21]1[CH:29]=O)[CH3:19].S(S([O-])=O)([O-])=O.[Na+].[Na+]>C(O)C.O.ClCCl>[Br:1][C:2]1[CH:9]=[C:8]([O:10][C:11]([F:12])([F:13])[F:14])[C:5]2[N:6]([CH3:7])[C:29]([C:21]3[N:20]([CH2:18][CH3:19])[C:24]4=[N:25][CH:26]=[CH:27][CH:28]=[C:23]4[CH:22]=3)=[N:15][C:4]=2[CH:3]=1

Participants

7

Reactant 3

HCID 24489Sodium DithioniteHCID 863401741-Ethyl-1H-pyrrolo[2,3-b]pyridine-2-carbaldehydeHCID 900275064-Bromo-N-methyl-2-nitro-6-(trifluoromethoxy)aniline

Product 1

HCID 1181589255-Bromo-2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-7-(trifluoromethoxy)-1H-benzo[d]imidazoleYield 33%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-bromo-N-methyl-2-nitro-6-(trifluoromethoxy)aniline (1.368 g, 4.34 mmol) and 1-ethyl-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde (0.756 g, 4.34 mmol) in ethanol (20 mL) was added sodium dithionite (2.67 g, 13.03 mmol) in water (10 mL). The mixture was flushed with nitrogen and then heated to 80° C. with stirring for 17 h. LCMS showed ˜52% conversion to the desired product with no starting material remaining. The reaction mixture was partitioned between aqueous hydrochloric acid (0.25 M, 100 mL) and extracted with dichloromethane (3×100 mL). The organics were combined, dried using a hydrophobic frit and evaporated under vacuum to give the crude product as a yellow solid. The sample was loaded in dichloromethane and purified by column chromatography on silica (100 g) using a gradient of 0-30% cyclohexane-ethyl acetate. The appropriate fractions were combined and evaporated in vacuo to give the required product (628 mg, 33%) as a yellow gum which solidified.

Workup

  1. customThe mixture was flushed with nitrogen
  2. customThe reaction mixture was partitioned between aqueous hydrochloric acid (0.25 M, 100 mL)
  3. extractionextracted with dichloromethane (3×100 mL)
  4. customdried
  5. customevaporated under vacuum
  6. customto give the crude product as a yellow solid
  7. custompurified by column chromatography on silica (100 g)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-3e0f8d363a764b248ea363d9f581faa0
Source dataset
uspto-grants-2015_09
Patent number
US09127003B2

Reaction notes

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