Ethyl orthoformate → 3-(4-((6-(difluoromethyl)pyridin-3-yl)methoxy)-3-methoxybenzyl)-6-iodo-3H-imidazo[4,5-b]pyridine

HRID 706524Notes

Reaction equation

HRID 706524 reaction equation
[F:1][CH:2]([F:29])[C:3]1[N:8]=[CH:7][C:6]([CH2:9][O:10][C:11]2[CH:26]=[CH:25][C:14]([CH2:15][NH:16][C:17]3[C:22]([NH2:23])=[CH:21][C:20]([I:24])=[CH:19][N:18]=3)=[CH:13][C:12]=2[O:27][CH3:28])=[CH:5][CH:4]=1.F[CH:31](F)C1N=CC(COC2C=CC(CN)=CC=2OC)=CC=1.C(OCC)(OCC)OCC.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[F:29][CH:2]([F:1])[C:3]1[N:8]=[CH:7][C:6]([CH2:9][O:10][C:11]2[CH:26]=[CH:25][C:14]([CH2:15][N:16]3[C:17]4=[N:18][CH:19]=[C:20]([I:24])[CH:21]=[C:22]4[N:23]=[CH:31]3)=[CH:13][C:12]=2[O:27][CH3:28])=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 31214Ethyl orthoformateHCID 521998p-Toluenesulfonic acid monohydrateHCID 118114096(4-((6-(Difluoromethyl)pyridin-3-yl)methoxy)-3-methoxyphenyl)methanamineHCID 118141875N2-(4-((6-(difluoromethyl)pyridin-3-yl)methoxy)-3-methoxybenzyl)-5-iodopyridine-2,3-diamine

Product 1

HCID 1181140493-(4-((6-(difluoromethyl)pyridin-3-yl)methoxy)-3-methoxybenzyl)-6-iodo-3H-imidazo[4,5-b]pyridineYield 99%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of N2-(4-((6-(difluoromethyl)pyridin-3-yl)methoxy)-3-methoxybenzyl)-5-iodopyridine-2,3-diamine [prepared from (4-((6-(difluoromethyl)pyridin-3-yl)methoxy)-3-methoxyphenyl)methanamine using the procedures described in Example 3-45-4 and Example 3-45-5] (3.10 g, 6.05 mmol) in ethanol (50 mL) was added triethyl orthoformate (3.0 mL, 18.02 mmol). The mixture was treated with p-toluenesulfonic acid monohydrate (50 mg, 262.86 μmol) and was heated to reflux. After 45 min, the mixture was allowed to cool to room temperature, resulting in the formation of a precipitate. The mixture was concentrated, and the residue dissolved in chloroform (150 mL). The solution was washed with saturated potassium carbonate solution, dried over magnesium sulfate, filtered, and concentrated to provide 3.15 g (99%) of 3-(4-((6-(difluoromethyl)pyridin-3-yl)methoxy)-3-methoxybenzyl)-6-iodo-3H-imidazo[4,5-b]pyridine as a brown solid.

Workup

  1. temperaturewas heated to reflux
  2. customresulting in the formation of a precipitate
  3. concentrationThe mixture was concentrated
  4. dissolutionthe residue dissolved in chloroform (150 mL)
  5. washThe solution was washed with saturated potassium carbonate solution
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-8e72867bc67444018890a8c48b4afeca
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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