Dimethylformamide → HCID 178512319, compound

HRID 895385Notes

Reaction equation

HRID 895385 reaction equation
ClC1C=C(Cl)C=CC=1NC(NC([C:22]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:23]=1[C:32]([F:35])([F:34])[F:33])CN1C=CN=C1)=NC#N.[C:36]([NH:38][C:39]([NH:41][C:42]1[CH:47]=[CH:46][C:45]([Cl:48])=[CH:44][C:43]=1[Cl:49])=S)#[N:37].CN(C)C[CH2:53][CH2:54][N:55]=[C:56]=[N:57][CH2:58][CH3:59].C[N:62](C=O)C>>[Cl:49][C:43]1[CH:44]=[C:45]([Cl:48])[CH:46]=[CH:47][C:42]=1[NH:41][C:39]([NH:62][CH2:59][CH:58]([C:22]1[CH:27]=[C:26]([C:28]([F:30])([F:29])[F:31])[CH:25]=[CH:24][C:23]=1[C:32]([F:35])([F:33])[F:34])[N:57]1[CH:53]=[CH:54][N:55]=[CH:56]1)=[N:38][C:36]#[N:37]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 21696870HCID 21696870, compoundHCID 178512255HCID 178512255, compound

Product 1

HCID 178512319HCID 178512319, compound

Procedure

1-(2,5-Bistrifuoromethylphenyl)-2-(benzimidazol-2-yl)ethylamine. To a stirred solution of 1,1,1,3,3,3-hexamethyldisilazane (2.91 mL, 13.8 mmol, 1.11 equiv) in 13 mL anhydrous THF at 0° C. was added n-butyllithium (5.20 mL of a 2.5 M solution in hexane, 13.0 mmol, 1.05 equiv). After 15 min, 2,5-bistrifluoromethylbenzaldehyde (2.04 g, 8.43 mmol) in anhydrous THF (4 mL) at 0° C. was slowly added, followed by chlorotrimethylsilane (1.73 mL, 1.6 mmol, 1.10 equiv). The mixture was partitioned between EtOAc and water, and the organic layer was washed with brine (3×50 mL), dried (Na2SO4), and concentrated to give Compound A as a solid. B. N-(2,4-Dichlorophenyl)-N′-[1-(2,5-bistrifluoromethylphenyl)-2-(imidazol-1-yl)-ethyl]-N″-cyanoguanidine. To a stirred solution of 1-(2,5-bistrifuoromethylphenyl)-2-(imidazol-1-yl)ethylamine (1.1 g, 3.4 mmol) in DMF at rt, N-cyano-N′-(2,4-dichlorophenyl)thiourea (1.1 g, 4.1 mmol) was added, followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (800 mg, 4.1 mmol). The mixture was allowed to stir at rt for 18 h and then partitioned between EtOAc and saturated ammonium chloride solution. The organic layer was separated and washed with saturated ammonium chloride solution (3×50 mL). The organic layer was dried and concentrated, and the residue was purified by silica gel column chromatography (EtOAc, MeOH, NH4OH; 95:5:0.1) to give a solid (350 mg). MS (ES): m/z 535 [M+H]+.

Workup

  1. custompartitioned between EtOAc and saturated ammonium chloride solution
  2. customThe organic layer was separated
  3. washwashed with saturated ammonium chloride solution (3×50 mL)
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. customthe residue was purified by silica gel column chromatography (EtOAc, MeOH, NH4OH; 95:5:0.1)

Sources & evidence

ORD record
ord-b3cd13362d12434b846d1b4f5fddb17d
Source dataset
uspto-grants-2005_07
Patent number
US06916813B2

Reaction notes

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