Hydrochloric Acid → 1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-N,N-bis(4-methoxybenzyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-4-amine

HRID 606091Notes

Reaction equation

HRID 606091 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([CH2:13][NH:14][C:15]3[C:20]([CH3:21])=[C:19]([CH3:22])[N:18]=[C:17]([N:23]([CH2:33][C:34]4[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=4)[CH2:24][C:25]4[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=4)[C:16]=3[NH2:42])[O:10][N:9]=2)=[CH:4][CH:3]=1.[CH:43](OCC)(OCC)OCC.Cl.Cl.N1C=CC=CC=1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([CH2:13][N:14]3[C:15]4[C:20]([CH3:21])=[C:19]([CH3:22])[N:18]=[C:17]([N:23]([CH2:24][C:25]5[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=5)[CH2:33][C:34]5[CH:35]=[CH:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=5)[C:16]=4[N:42]=[CH:43]3)[O:10][N:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 31214Ethyl orthoformate2×HCID 10176127Pyridinium chlorideHCID 69453189N4-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-N2,N2-bis(4-methoxybenzyl)-5,6-dimethylpyridine-2,3,4-triamine

Product 1

HCID 670414341-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-N,N-bis(4-methoxybenzyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-4-amineYield 32.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

N4-{[3-(4-Fluorophenyl)isoxazol-5-yl]methyl}-N2,N2-bis(4-methoxybenzyl)-5,6-dimethylpyridine-2,3,4-triamine (6.00 g, 10.6 mmol), triethyl orthoformate (2.6 mL, 16 mmol), concentrated hydrochloride acid (0.2 mL), and toluene (30 mL) were combined at heated at reflux for 24 hours. An analysis by HPLC indicated the reaction was incomplete. Therefore, pyridine hydrochloride (0.25 g) was added, and the reaction vessel was fitted with a Dean-Stark trap. The reaction was heated at reflux for an additional 1.8 days, and additional triethyl orthoformate (1 mL) was added and heating was resumed. After the reaction was heated for a total of three days, it was allowed to cool to room temperature, and concentrated under reduced pressure. The residue was dissolved in dichloromethane, and the resulting solution was washed sequentially with aqueous potassium carbonate, water, and brine; dried over magnesium sulfate; and filtered. The solution was purified by column chromatography on silica gel (eluting with 5% ethyl acetate in dichloromethane) to provide 2.0 g of 1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-N,N-bis(4-methoxybenzyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-4-amine as a pale yellow solid.

Workup

  1. temperatureat heated
  2. temperatureat reflux for 24 hours
  3. customthe reaction vessel was fitted with a Dean-Stark trap
  4. temperatureThe reaction was heated
  5. temperatureat reflux for an additional 1.8 days
  6. temperatureheating
  7. temperatureAfter the reaction was heated for a total of three days, it
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe residue was dissolved in dichloromethane
  10. washthe resulting solution was washed sequentially with aqueous potassium carbonate, water, and brine
  11. dry with materialdried over magnesium sulfate
  12. filtrationand filtered
  13. customThe solution was purified by column chromatography on silica gel (eluting with 5% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-02a7c375e61d4b7792ec21bd082dd8e9
Source dataset
uspto-grants-2011_03
Patent number
US07915281B2

Reaction notes

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