Methanol → HCID 57743074, compound

HRID 2043676Notes

Reaction equation

HRID 2043676 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][NH:8][C:9]2[C:10]([N+:24]([O-])=O)=[C:11]([CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[N:19]=2)[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:5][CH:4]=1.[CH3:29]O>[Ni]>[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]2[C:9]3=[N:19][C:18]([C:20]([F:23])([F:22])[F:21])=[CH:17][C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:10]3[N:24]=[CH:29]2)=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 887MethanolHCID 57742994HCID 57742994, compound

Product 1

HCID 57743074HCID 57743074, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 935NickelCatalyst

Conditions

Temperature
150 °C

Procedure

Ethyl 2-[(4-methoxybenzyl)amino]-3-nitro-6-(trifluoromethyl)isonicotinate x193 (2.6 g, 6.5 mmol) is dissolved in methanol (100 ml), and Raney nickel (0.8 g) is added. The starting compound is hydrogenated in a Parr apparatus under a hydrogen pressure of 3 atm until the conversion of x193 is complete (1.5-2 h). The catalyst is filtered off and washed with methanol. The filtrate is evaporated to dryness. Triethyl orthoformate (100 ml) and p-toluene sulfonic acid (0.15 g) are added. The flask is equipped with a reflux condenser. The apparatus is flushed with argon, and the obtained reaction mixture is heated under vigorous stirring to 150° C. for 6 h. The reaction solution is evaporated in vacuum. The residue is partitioned between dichloromethane and a saturated aqueous solution of NaHCO3. The organic layer is dried with anhydrous sodium sulfate and evaporated. The target product is purified by chromatography on silicagel (dichloromethane/acetone) to afford 1.5 g of ethyl 3-(4-methoxybenzyl)-5-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine-7-carboxylate x196.

Workup

  1. custom(1.5-2 h)
  2. filtrationThe catalyst is filtered off
  3. washwashed with methanol
  4. customThe filtrate is evaporated to dryness
  5. additionTriethyl orthoformate (100 ml) and p-toluene sulfonic acid (0.15 g) are added
  6. customThe flask is equipped with a reflux condenser
  7. customThe apparatus is flushed with argon
  8. customthe obtained reaction mixture
  9. temperatureis heated
  10. customThe reaction solution is evaporated in vacuum
  11. customThe residue is partitioned between dichloromethane
  12. dry with materialThe organic layer is dried with anhydrous sodium sulfate
  13. customevaporated
  14. customThe target product is purified by chromatography on silicagel (dichloromethane/acetone)

Sources & evidence

ORD record
ord-29508d13f6764132a00530746ecc0fb5
Source dataset
uspto-grants-2013_11
Patent number
US08586623B2

Reaction notes

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