1-Hydroxybenzotriazole → N-(6-Cyano-1H-benzimidazol-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide

HRID 1403072Notes

Reaction equation

HRID 1403072 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:10][CH:9]2[C:11]([OH:13])=O)[CH:5]=[CH:6][CH:7]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl.[NH2:37][C:38]1[NH:39][C:40]2[CH:46]=[C:45]([C:47]#[N:48])[CH:44]=[CH:43][C:41]=2[N:42]=1>CN(C=O)C>[C:47]([C:45]1[CH:44]=[CH:43][C:41]2[N:42]=[C:38]([NH:37][C:11]([CH:9]3[CH2:10][CH:8]3[C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[O:13])[NH:39][C:40]=2[CH:46]=1)#[N:48]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 218646592-(3-Fluorophenyl)cyclopropanecarboxylic acidHCID 867295832-Amino-3H-benzoimidazole-5-carbonitril hydrochloride

Product 1

HCID 71513846N-(6-Cyano-1H-benzimidazol-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(3-Fluoro-phenyl)-cyclopropanecarboxylic acid 2 (90 mg, 0.50 mmol) was dissolved in 10 ml DMF. 115 mg (0.6 mmol) 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and 81 mg (0.6 mmol) 1-Hydroxybenzotriazole (HOBT) were added. The mixture was stirred for 30 min at room temperature (RT). Then 97 mg (0.5 mmol) 2-Amino-3H-benzoimidazole-5-carbonitril hydrochloride 1 were added to the mixture, which was stirred for 16 h at RT. After removing the solvent in vacuo, 20 ml water were added, whereupon the mixture was extracted 3 times with 50 ml acetic acid ethylester. The organic phases were combined, dried with sodium sulfate, and evaporated to dryness. The residue was separated via preparative HPLC. The resulting clean fractions were concentrated and lyophilized. 91 mg (57%) of a colorless, amorphous solid 3 were obtained.

Workup

  1. stirringwas stirred for 16 h at RT
  2. customAfter removing the solvent in vacuo, 20 ml water
  3. additionwere added, whereupon the mixture
  4. extractionwas extracted 3 times with 50 ml acetic acid ethylester
  5. dry with materialdried with sodium sulfate
  6. customevaporated to dryness
  7. customThe residue was separated via preparative HPLC
  8. concentrationThe resulting clean fractions were concentrated

Sources & evidence

ORD record
ord-ddf8606d781d421da62a240339fd63e4
Source dataset
uspto-grants-2014_12
Patent number
US08912202B2

Reaction notes

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