Triethyl orthoacetate → 2,6,7-trimethyl-4-phenoxy-1-[2-(3-pyridin-3-ylpropoxy)ethyl]-1H-imidazo[4,5-c]pyridine

HRID 1245904Notes

Reaction equation

HRID 1245904 reaction equation
[CH3:1][C:2]1[C:3]([NH:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][CH2:23][C:24]2[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=2)=[C:4]([NH2:16])[C:5]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][C:7]=1[CH3:8].Cl.N1C=CC=[CH:33][CH:32]=1.C(OCC)(OCC)(OCC)C>C1(C)C=CC=CC=1>[CH3:32][C:33]1[N:17]([CH2:18][CH2:19][O:20][CH2:21][CH2:22][CH2:23][C:24]2[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=2)[C:3]2[C:2]([CH3:1])=[C:7]([CH3:8])[N:6]=[C:5]([O:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:4]=2[N:16]=1

Participants

5

Reactant 3

HCID 66221Triethyl orthoacetateHCID 10176127Pyridinium chlorideHCID 691854145,6-dimethyl-2-phenoxy-N4-[2-(3-pyridin-3-ylpropoxy)ethyl]pyridine-3,4-diamine

Product 1

HCID 219131992,6,7-trimethyl-4-phenoxy-1-[2-(3-pyridin-3-ylpropoxy)ethyl]-1H-imidazo[4,5-c]pyridine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
99 °C

Procedure

A solution of 5,6-dimethyl-2-phenoxy-N4-[2-(3-pyridin-3-ylpropoxy)ethyl]pyridine-3,4-diamine (12 g) in toluene (300 ml) from Part C was combined with pyridine HCl (0.08 g) and triethyl orthoacetate (8.4 ml). Under a nitrogen atmosphere, the reaction mixture was heated to reflux (99° C.) for 1.5 hours. TLC and HPLC analysis indicated that the reaction was complete. The solvent was removed under reduced pressure. The resulting yellow oil was dissolved in dichloromethane and washed once with saturated potassium carbonate, 3 times with water, and 3 times with brine. The combined organic layers were dried with magnesium sulfate and concentrated under reduced pressure. The resulting yellow oil darkened slightly after being dried under vacuum at 70° C. overnight. The product was purified by column chromatography over silica using 95/5 ethyl acetate/methanol as the eluant. The product was dried and then triturated with diethyl ether to yield a white solid that was dried under vacuum at 80° C. overnight. NMR analysis of the dried solid indicated a pure product.

Workup

  1. temperatureUnder a nitrogen atmosphere, the reaction mixture was heated
  2. customThe solvent was removed under reduced pressure
  3. dissolutionThe resulting yellow oil was dissolved in dichloromethane
  4. washwashed once with saturated potassium carbonate, 3 times with water, and 3 times with brine
  5. dry with materialThe combined organic layers were dried with magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customafter being dried under vacuum at 70° C. overnight
  8. customThe product was purified by column chromatography over silica using 95/5 ethyl acetate/methanol as the eluant
  9. customThe product was dried
  10. customtriturated with diethyl ether
  11. customto yield a white solid
  12. customthat was dried under vacuum at 80° C. overnight

Sources & evidence

ORD record
ord-5c2f11ea198546699ecfb09c2447dcd2
Source dataset
uspto-grants-2006_10
Patent number
US07125890B2

Reaction notes

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