Triethylamine → HCID 21973845, compound

HRID 11377Notes

Reaction equation

HRID 11377 reaction equation
[NH2:1][C:2]1[C:3]([O:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:4][C:5]([CH3:18])=[C:6]([CH3:17])[C:7]=1[NH:8][CH2:9][C:10]([NH:13][C:14](=[O:16])[CH3:15])([CH3:12])[CH3:11].C(N(CC)CC)C.[CH2:33]([O:35][CH2:36][C:37](Cl)=O)[CH3:34]>C(Cl)Cl>[CH2:33]([O:35][CH2:36][C:37]1[N:8]([CH2:9][C:10]([NH:13][C:14](=[O:16])[CH3:15])([CH3:11])[CH3:12])[C:7]2[C:6]([CH3:17])=[C:5]([CH3:18])[N:4]=[C:3]([O:19][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:2]=2[N:1]=1)[CH3:34]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 84189Ethoxyacetyl chlorideHCID 21973814HCID 21973814, compound

Product 1

HCID 21973845HCID 21973845, compoundYield 45.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of N-{2-[(3-amino-5,6-dimethyl-2-phenoxypyridin-4-yl)amino]-1,1-dimethylethyl}acetamide (1.80 g, 5.23 mmol) in 50 mL of CH2Cl2 was cooled to 0° C., under N2, and treated with triethylamine (728 μL, 5.23 mmol) and ethoxyacetyl chloride (574 μL, 5.23 mmol). After stirring overnight, the reaction mixture was concentrated under reduced pressure. The resulting syrup was taken up in 50 mL of EtOH and treated with 3 mL of triethylamine. The solution was heated to reflux for 4 d. The reaction mixture was then concentrated and redissolved in 50 mL of xylenes and treated with pyridinium hydrochloride (0.5 g) and the mixture was heated to reflux for 4 d. The reaction mixture was concentrated and taken up in 100 mL of EtOAc and washed with saturated NaHCO3 solution, H2O (2×) and brine. The organic portion was dried over Na2SO4 and concentrated. The resulting syrup was purified by column chromatography (SiO2, 80% EtOAc/hexanes) to give N-{2-[2-(ethoxymethyl)-6,7-dimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl]-1,1-dimethylethyl}acetamide (980 mg) as a mustard colored foam.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. additiontreated with 3 mL of triethylamine
  3. temperatureThe solution was heated
  4. temperatureto reflux for 4 d
  5. concentrationThe reaction mixture was then concentrated
  6. dissolutionredissolved in 50 mL of xylenes
  7. additiontreated with pyridinium hydrochloride (0.5 g)
  8. temperaturethe mixture was heated
  9. temperatureto reflux for 4 d
  10. concentrationThe reaction mixture was concentrated
  11. washwashed with saturated NaHCO3 solution, H2O (2×) and brine
  12. dry with materialThe organic portion was dried over Na2SO4
  13. concentrationconcentrated
  14. customThe resulting syrup was purified by column chromatography (SiO2, 80% EtOAc/hexanes)

Sources & evidence

ORD record
ord-b80539dc2ef344d398c44bf5d354c5d7
Source dataset
uspto-grants-2006_08
Patent number
US07098221B2

Reaction notes

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