Dichloromethane → HCID 57545308, compound

HRID 2383204Notes

Reaction equation

HRID 2383204 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:24][O:25][CH2:26][CH3:27])[N:14]([CH2:15][C:16]([NH:19][S:20]([CH3:23])(=[O:22])=[O:21])([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[C:7]([O:28]CC3C=CC=CC=3)[CH:6]=[CH:5][C:4]=2[N:3]=1.[H][H].ClCCl.[OH-].[NH4+]>C(O)C.[Pd].CO>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:24][O:25][CH2:26][CH3:27])[N:14]([CH2:15][C:16]([NH:19][S:20]([CH3:23])(=[O:22])=[O:21])([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[C:7]([OH:28])[CH:6]=[CH:5][C:4]=2[N:3]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 14923Ammonium HydroxideHCID 57545281HCID 57545281, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 57545308HCID 57545308, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

N-[2-(4-Amino-8-benzyloxy-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)-1,1-dimethylethyl]methanesulfonamide (1.16 g, 2.33 mmol) was dissolved in 50 mL of ethanol and 10% palladium on carbon (0.46 g) was added. The mixture was shaken overnight under 50 psi (3.4×105 Pa) of hydrogen. Dichloromethane (100 mL) and methanol (100 mL) were added and reaction was filtered through CELITE filter agent. The filter cake was washed with 200 mL of 1:1 dichloromethane:methanol. The filtrate was concentrated under reduced pressure to give a white solid. The solid was precipitated from a minimum amount of ethanol and then redissolved in dichloromethane containing a minimum amount of methanol. Aqueous ammonium hydroxide was added. The two phases were mixed by shaking and then separated. The organic fraction was discarded and the aqueous fraction was extracted with four portions of dichloromethane followed by two portions of ethyl acetate. The combined organic fractions were concentrated. The volume of the aqueous fraction was reduced, and a precipitate formed. The aqueous fraction was made basic by the addition of aqueous ammonium hydroxide and the resulting precipitate was recovered by filtration. The solid precipitate was combined with the residue from the organic fraction to give 0.75 g of crude product. This material was purified by column chromatography on a HORIZON HPFC system. A silica gel cartridge was used with the eluent being a gradient of 30-50% CMA in chloroform to provide 0.57 g of N-[2-(4-amino-2-ethoxymethyl-8-hydroxy-1H-imidazo[4,5-c]quinolin-1-yl)-1,1-dimethylethyl]methanesulfonamide as a white powder, m.p. 252-254° C.

Workup

  1. customreaction
  2. filtrationwas filtered through CELITE
  3. filtrationfilter agent
  4. washThe filter cake was washed with 200 mL of 1:1 dichloromethane
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customto give a white solid
  7. customThe solid was precipitated from a minimum amount of ethanol
  8. dissolutionredissolved in dichloromethane containing a minimum amount of methanol
  9. additionAqueous ammonium hydroxide was added
  10. additionThe two phases were mixed
  11. customseparated
  12. extractionthe aqueous fraction was extracted with four portions of dichloromethane
  13. concentrationThe combined organic fractions were concentrated
  14. customa precipitate formed
  15. filtrationthe resulting precipitate was recovered by filtration
  16. customto give 0.75 g of crude product
  17. customThis material was purified by column chromatography on a HORIZON HPFC system

Sources & evidence

ORD record
ord-fea3ebb7ff8e4fc2b0058b76a3af9305
Source dataset
uspto-grants-2012_09
Patent number
US08263594B2

Reaction notes

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