4-Toluenesulfonyl chloride → HCID 10039789, compound

HRID 2426348Notes

Reaction equation

HRID 2426348 reaction equation
ClC1C=C(C=CC=1)C(OO)=O.[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.ClCCl.O>[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 962WaterSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

3-Chloroperoxybenzoic acid (mCPBA) (32.7 g of 77% pure material, 146 mmol) was added over a period of five minutes to a solution of 2-chloromethyl-1-(2-methylpropyl)-1H-imidazo[4,5-c]quinoline (20.0 g, 73.1 mmol) in chloroform (500 mL); the reaction mixture was stirred at ambient temperature for one hour. Ammonium hydroxide (200 mL) was added, and then p-toluenesulfonyl chloride (16.7 g, 87.7 mmol) was added in portions over a period of 10 minutes. The reaction mixture was stirred at ambient temperature for one hour, and then water (200 mL) was added. The aqueous layer was separated and extracted with dichloromethane (2×200 mL). The combined organic fractions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 32 g of crude product as a tan solid. The crude product was dissolved in dichloromethane (50 mL), and the resulting solution was divided into two portions. Each portion was purified by column chromatography using a HORIZON HPFC system (an automated, modular high-performance flash purification product available from Biotage, Inc, Charlottesville, Va., USA) using a FLASH 65I silica cartridge (also available from Biotage, Inc.) (eluting with ethyl acetate:methanol in a gradient from 98:2 to 85:15) to provide 11.24 g of 2-chloromethyl-1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine as a tan solid.

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for one hour
  2. customThe aqueous layer was separated
  3. extractionextracted with dichloromethane (2×200 mL)
  4. dry with materialThe combined organic fractions were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto provide 32 g of crude product as a tan solid
  8. customEach portion was purified by column chromatography
  9. custommodular high-performance flash purification product available from Biotage, Inc, Charlottesville, Va
  10. wash) (eluting with ethyl acetate

Sources & evidence

ORD record
ord-03cc8ff652be4060a1ca6887c71d10b3
Source dataset
uspto-grants-2011_06
Patent number
US07968563B2

Reaction notes

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