4-Toluenesulfonyl chloride → HCID 10039789, compound

HRID 1907932Notes

Reaction equation

HRID 1907932 reaction equation
C1C=C(Cl)C=C(C(OO)=O)C=1.[Cl:12][CH2:13][C:14]1[N:15]([CH2:27][CH:28]([CH3:30])[CH3:29])[C:16]2[C:25]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[N:19]=[CH:18][C:17]=2[N:26]=1.[OH-].[NH4+:32].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl.CO.ClCCl>[Cl:12][CH2:13][C:14]1[N:15]([CH2:27][CH:28]([CH3:30])[CH3:29])[C:16]2[C:25]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[N:19]=[C:18]([NH2:32])[C:17]=2[N:26]=1

Participants

8

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 67052403HCID 67052403, compound

Product 1

HCID 10039789HCID 10039789, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

3-Chlioroperoxybenzoic acid (mCPBA) (16.4 g of 77% max, 73.1 mmol) was added to a solution of 2-chloromethyl-1-(2-methylpropyl)-1H-imidazo[4,5-c]quinoline (10 g, 36.5 mmol) in chloroform (250 mL). The reaction mixture was stirred at ambient temperature overnight. Ammonium hydroxide (100 mL) was added and the reaction was stirred vigorously for 15 minutes. Para-toluenesulfonyl chloride (8.4 g, 43.8 mmol) was added in portions over a period of 10 minutes. The reaction mixture was stirred at ambient temperature for 1 hour and then filtered to remove a precipitate. The filtrate was transferred to a separatory funnel and the layers were separated. The aqueous layer was extracted with dichloromethane (2×100 mL). The combined organics were dried over magnesium sulfate, filtered through a layer of CELITE filter aid, and then concentrated under reduced pressure to provide 16 g of crude product as a yellow foam. The foam was dissolved in 10% methanol in dichloromethane (20 mL). The solution was divided and loaded onto two FLASH 40+M silica cartridges (90 g), (available from Biotage, Inc, Charlottesville, Va., USA). The cartridges were eluted sequentially with 1 L 1:1 ethyl acetate:hexanes, 2% methanol in 1:1 ethyl acetate:hexanes, and 5% methanol in 1:1 ethyl acetate:hexanes. The fractions containing product were combined and then concentrated under reduced pressure to provide 6.4 g of 2-chloromethyl-1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine as an orange foam.

Workup

  1. stirringthe reaction was stirred vigorously for 15 minutes
  2. stirringThe reaction mixture was stirred at ambient temperature for 1 hour
  3. filtrationfiltered
  4. customto remove a precipitate
  5. customThe filtrate was transferred to a separatory funnel
  6. customthe layers were separated
  7. extractionThe aqueous layer was extracted with dichloromethane (2×100 mL)
  8. dry with materialThe combined organics were dried over magnesium sulfate
  9. filtrationfiltered through a layer of CELITE
  10. filtrationfilter aid
  11. concentrationconcentrated under reduced pressure
  12. customto provide 16 g of crude product as a yellow foam
  13. washThe cartridges were eluted sequentially with 1 L 1:1 ethyl acetate
  14. additionThe fractions containing product
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-22c004f1787c4617af2e2dee296ed5dd
Source dataset
uspto-grants-2013_12
Patent number
US08598192B2

Reaction notes

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