Cyanogen Bromide → [6-(5-Amino-[1,3,4]oxadiazol-2-yl)-4-fluoro-1H-benzoimidazol-5-yl]-(4-bromo-2-methyl-phenyl)-amine

HRID 1925836Notes

Reaction equation

HRID 1925836 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:19]([NH:21][NH2:22])=[O:20])=[CH:11][C:12]3[NH:16][CH:15]=[N:14][C:13]=3[C:17]=2[F:18])=[C:4]([CH3:23])[CH:3]=1.[N:24]#[C:25]Br.C([O-])(O)=O.[Na+]>O1CCOCC1.C(Cl)Cl.O.[Cl-].[Na+].O>[NH2:24][C:25]1[O:20][C:19]([C:10]2[C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=3[CH3:23])=[C:17]([F:18])[C:13]3[N:14]=[CH:15][NH:16][C:12]=3[CH:11]=2)=[N:21][N:22]=1

Participants

8

Reactant 3

HCID 10476Cyanogen BromideHCID 516892Sodium BicarbonateHCID 668979206-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid hydrazide

Product 1

HCID 10150820[6-(5-Amino-[1,3,4]oxadiazol-2-yl)-4-fluoro-1H-benzoimidazol-5-yl]-(4-bromo-2-methyl-phenyl)-amineYield 55%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

6-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid hydrazide 20a (0.041 g, 0.109 mmol) is suspended in 1,4-dioxane (1.5 mL) and 36 μL of a 3 M solution of cyanogen bromide in methylene chloride is added. NaHCO3 (9 mg, 0.109 mmol) in water (1.5 mL) is then added. After 16 hours, the reaction mixture is diluted with water and brine and extracted with THF. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. Purification by FCC eluted with 98:2 ethyl acetate:MeOH provides 24 mg (55%) of pure desired product as a yellow solid: LC/MS ESI (+) m/z 403, 405 (M+Br pattern) detected;

Workup

  1. extractionextracted with THF
  2. dry with materialThe combined organic extracts are dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customPurification by FCC
  5. washeluted with 98:2 ethyl acetate

Sources & evidence

ORD record
ord-fdf0baf4a12f4f70bca10ea56708e751
Source dataset
uspto-grants-2012_05
Patent number
US08178693B2

Reaction notes

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