4-Toluenesulfonyl chloride → HCID 66958565, compound

HRID 1364040Notes

Reaction equation

HRID 1364040 reaction equation
C1C=C(Cl)C=C(C(OO)=[O:9])C=1.[CH3:12][S:13]([N:16]1[CH2:33][CH2:32][CH2:31][N:19]2[C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:23]=[CH:22][C:21]=3[N:30]=[C:18]2[CH2:17]1)(=[O:15])=[O:14].[OH-].[NH4+].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[CH3:12][S:13]([N:16]1[CH2:33][CH2:32][CH2:31][N:19]2[C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[N+:23]([O-:9])=[CH:22][C:21]=3[N:30]=[C:18]2[CH2:17]1)(=[O:15])=[O:14]

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acid4×HCID 66958192HCID 66958192, compound

Product 1

HCID 66958565HCID 66958565, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

mCPBA (2.55 g of 77%, 11.38 mmol) was added to a suspension of 9-(methylsulfonyl)-9,10,11,12-tetrahydro-8H-[1,4]diazepino[1′,2′:1,2]imidazo[4,5-c]quinoline (3.0 g, 9.5 mmol) in chloroform, and the reaction was stirred for 30 minutes at ambient temperature. The reaction was incomplete as determined by LC/MS analysis. Additional mCPBA (approximately 0.5 equivalent) was added twice, and the reaction was stirred overnight. The solvent was removed under reduced pressure, and a solution of potassium hydroxide in methanol was added to adjust to pH 7.5. The methanol was removed under reduced pressure, and residue was dissolved in chloroform. Additional mCPBA (1.2 equivalents) was added, and the reaction was stirred for two hours. Additional mCPBA was added, and the reaction was stirred overnight at ambient temperature. Ammonium hydroxide (15 mL) and p-toluenesulfonyl chloride (1.99 g, 10.4 mmol) were added, and the reaction was stirred at ambient temperature for two hours. The organic layer was separated, concentrated under reduced pressure, and purified by normal phase preparative HPLC on silica gel (eluting with 2 N ammonia in methanol/chloroform in a 42-minute gradient from 0:100 to 25:75). The resulting solid was recrystallized from 5:2:1 acetonitrile/ethanol/methanol to provide 9-(methylsulfonyl)-5-oxido-9,10,11,12-tetrahydro-8H-[1,4]diazepino[1′,2′:1,2]imidazo[4,5-c]quinoline, which was dissolved in chloroform, treated with ammonium hydroxide and p-toluenesulfonyl chloride, and purified by chromatography and recrystallization again as described above to provide 161 mg of 9-(methylsulfonyl)-9,10,11,12-tetrahydro-8H-[1,4]diazepino[1′,2′:1,2]imidazo[4,5-c]quinolin-6-amine as a white powder, mp 280° C.

Workup

  1. stirringthe reaction was stirred overnight
  2. customThe solvent was removed under reduced pressure
  3. additiona solution of potassium hydroxide in methanol was added
  4. customThe methanol was removed under reduced pressure, and residue
  5. dissolutionwas dissolved in chloroform
  6. stirringthe reaction was stirred for two hours
  7. stirringthe reaction was stirred overnight at ambient temperature
  8. stirringthe reaction was stirred at ambient temperature for two hours
  9. customThe organic layer was separated
  10. concentrationconcentrated under reduced pressure
  11. custompurified by normal phase preparative HPLC on silica gel (
  12. washeluting with 2 N ammonia in methanol/chloroform in a 42-minute gradient from 0:100 to 25:75)
  13. customThe resulting solid was recrystallized from 5:2:1 acetonitrile/ethanol/methanol

Sources & evidence

ORD record
ord-ae135c583b4d45ca8644021b8a62eae4
Source dataset
uspto-grants-2011_02
Patent number
US07888349B2

Reaction notes

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