Ethyl orthoformate → 5-iodo-1-(1-(3-methoxy-4-((6-(trifluoromethyl)pyridin-3-yl)methoxy)phenyl)ethyl)-1H-benzo[d]imidazole

HRID 2178394Notes

Reaction equation

HRID 2178394 reaction equation
[I:1][C:2]1[CH:3]=[C:4]([NH2:31])[C:5]([NH:8][CH:9]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]3[CH:20]=[N:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=3)=[C:13]([O:29][CH3:30])[CH:12]=2)[CH3:10])=[CH:6][CH:7]=1.Cl[CH2:33]C1C=CC(C(F)(F)F)=NC=1.C(OCC)(OCC)OCC.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[I:1][C:2]1[CH:7]=[CH:6][C:5]2[N:8]([CH:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]4[CH:20]=[N:21][C:22]([C:25]([F:26])([F:28])[F:27])=[CH:23][CH:24]=4)=[C:13]([O:29][CH3:30])[CH:12]=3)[CH3:10])[CH:33]=[N:31][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 31214Ethyl orthoformateHCID 521998p-Toluenesulfonic acid monohydrateHCID 27738105-(Chloromethyl)-2-(trifluoromethyl)pyridineHCID 1181140144-iodo-N1-(1-(3-methoxy-4-((6-(trifluoromethyl)pyridin-3-yl)methoxy)phenyl)ethyl)benzene-1,2-diamine

Product 1

HCID 1181140745-iodo-1-(1-(3-methoxy-4-((6-(trifluoromethyl)pyridin-3-yl)methoxy)phenyl)ethyl)-1H-benzo[d]imidazoleYield 76%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To stirred solution of 4-iodo-N1-(1-(3-methoxy-4-((6-(trifluoromethyl)pyridin-3-yl)methoxy)phenyl)ethyl)benzene-1,2-diamine [prepared from 5-(chloromethyl)-2-(trifluoromethyl)pyridine using the procedures described in Example 3-45-1 through Example 3-45-5] (1.04 g, 1.91 mmol) in ethanol (30 mL) was added triethyl orthoformate (1.0 mL, 5.89 mmol) and p-toluenesulfonic acid monohydrate (0.025 g, 0.13 mmol). The yellow solution was heated to reflux. After 30 min, the mixture was allowed to cool to room temperature and was concentrated to provide a yellow oil. Chromatographic purification (CombiFlash, 24 g SiO2 gold column, 1-5% methanol/dichloromethane elute) afforded 0.803 g (76%) of 5-iodo-1-(1-(3-methoxy-4-((6-(trifluoromethyl)pyridin-3-yl)methoxy)phenyl)ethyl)-1H-benzo[d]imidazole as a yellow solid.

Workup

  1. temperatureThe yellow solution was heated to reflux
  2. concentrationwas concentrated
  3. customto provide a yellow oil
  4. customChromatographic purification (CombiFlash, 24 g SiO2 gold column, 1-5% methanol/dichloromethane elute)

Sources & evidence

ORD record
ord-904c64451ff04222bf0d8036fdcba3d1
Source dataset
uspto-grants-2015_06
Patent number
US09067914B1

Reaction notes

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