4-Toluenesulfonyl chloride → HCID 57447065, compound

HRID 2366678Notes

Reaction equation

HRID 2366678 reaction equation
[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:18][CH2:19][CH2:20][C:21]([NH2:23])=[O:22])[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:17]=1)[CH3:2].C1C=C(Cl)C=C(C(OO)=O)C=1.[OH-].[NH4+:36].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>ClCCl>[NH2:36][C:9]1[C:8]2[N:17]=[C:5]([CH2:4][O:3][CH2:1][CH3:2])[N:6]([CH2:18][CH2:19][CH2:20][C:21]([NH2:23])=[O:22])[C:7]=2[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N:10]=1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acid2×HCID 69506692HCID 69506692, compound

Product 1

HCID 57447065HCID 57447065, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-[2-(Ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butanamide (4.3 g, 14 mmol) was treated with mCPBA (6.1 g, 27 mmol), concentrated ammonium hydroxide (50 mL of 29%), and p-toluenesulfonyl chloride (4.6 g, 24 mmol) according to a modification of the method described in Part E of Example 3. The mCPBA addition was carried out at 0° C., and the reaction was carried out in dichloromethane (150 mL). At the end of the reaction the layers were separated, and saturated aqueous sodium bicarbonate (100 mL) and 5% aqueous sodium hydroxide (10 mL) were added to the organic layer. The aqueous layer was extracted with dichloromethane (1.3 L), and the combined extracts were dried over potassium carbonate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluting with 90:10 dichloromethane:methanol containing 4 mL/L of ammonium hydroxide) followed by recrystallization five times from ethanol containing a small amount of water. The resulting solid was recrystallized from water:acetonitrile (5:L), dried overnight in a vacuum oven at 70° C., triturated with 25% aqueous ammonium hydroxide, diluted with water, isolated by filtration, recrystallized from ethanol:water, and dried overnight in a vacuum oven at 70° C. to provide 0.4704 g of 4-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]butanamide as tan crystals, mp 233-235° C.

Workup

  1. customwas carried out at 0° C.
  2. customAt the end of the reaction the layers
  3. customwere separated
  4. additionsaturated aqueous sodium bicarbonate (100 mL) and 5% aqueous sodium hydroxide (10 mL) were added to the organic layer
  5. extractionThe aqueous layer was extracted with dichloromethane (1.3 L)
  6. dry with materialthe combined extracts were dried over potassium carbonate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by column chromatography on silica gel (eluting with 90:10 dichloromethane:methanol containing 4 mL/L of ammonium hydroxide)
  10. customfollowed by recrystallization five times from ethanol containing a small amount of water
  11. customThe resulting solid was recrystallized from water
  12. dry with materialacetonitrile (5:L), dried overnight in a vacuum oven at 70° C.
  13. customtriturated with 25% aqueous ammonium hydroxide
  14. additiondiluted with water
  15. customisolated by filtration
  16. customrecrystallized from ethanol
  17. dry with materialwater, and dried overnight in a vacuum oven at 70° C.

Sources & evidence

ORD record
ord-c5f94baa3d2c4296a65efcc9c83fb246
Source dataset
uspto-grants-2014_04
Patent number
US08697873B2

Reaction notes

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