Dimethylformamide → 1H-Benzimidazole-7-carbonitrile, 5-(trifluoromethyl)-

HRID 913910Notes

Reaction equation

HRID 913910 reaction equation
Br[C:2]1[C:7]2[NH:8][CH:9]=[N:10][C:6]=2[CH:5]=[C:4]([C:11]([F:14])([F:13])[F:12])[CH:3]=1.[CH3:15][N:16](C)C=O>O.[C-]#N.[Zn+2].[C-]#N.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:12][C:11]([F:14])([F:13])[C:4]1[CH:3]=[C:2]([C:15]#[N:16])[C:7]2[NH:8][CH:9]=[N:10][C:6]=2[CH:5]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 178506062HCID 178506062, compound

Product 1

HCID 1785098911H-Benzimidazole-7-carbonitrile, 5-(trifluoromethyl)-Yield 45%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Procedure

A red suspension of 7-Bromo-5-(trifluoromethyl)-1H-benzo[d]imidazole (270 mg, 1.02 mmol), zinc cyanide (1.12 mmol), and PdCl2(dppf) (0.06 mmol) in Water (3 ml) and dimethylformamide (10 ml) was heated with stirring under argon for 2 h. At the end, LC-MS analysis revealed completion of the reaction. The reaction mixture was cooled to ambient temperature and was subjected to preparative HPLC (8 injections using HPLC method 14). Fractions containing the required product were combined and evaporated in vacuo to give 97 mg (45% yield). 1H NMR (CD3OD, 500 MHz) δ 7.88 (s, 1H), 8.21 (s, 1H), 8.54 (s, 1H); IR (KBr) 2229 (CN stretching); LC/MS (HPLC method 9): tR=1.8 min, 212(MH)+.

Workup

  1. temperaturewas heated
  2. customcompletion of the reaction

Sources & evidence

ORD record
ord-1592be1ecc054d68bea558903836dc37
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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