4-Toluenesulfonyl chloride → HCID 69177518, compound

HRID 1373952Notes

Reaction equation

HRID 1373952 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:14]([NH:15][CH:16]([CH3:18])[CH3:17])[C:13]([CH2:19][CH2:20][CH3:21])=[N:12][C:7]=3[CH:8]=[N:9][C:10]=2[CH:11]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.[OH-].[NH4+:34].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:14]([NH:15][CH:16]([CH3:17])[CH3:18])[C:13]([CH2:19][CH2:20][CH3:21])=[N:12][C:7]=3[C:8]([NH2:34])=[N:9][C:10]=2[CH:11]=1

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 21075799HCID 21075799, compound

Product 1

HCID 69177518HCID 69177518, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

A solution of N-(7-bromo-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)isopropylamine (9.10 g, 26.2 mmol) in 200 mL of chloroform was placed under an atmosphere of nitrogen and cooled in an ice water bath. The solution was treated with MCPBA (8.28 g, 28.8 mmol, 77% max) and allowed to slowly come to ambient temperature. After 2 h, LC/MS and HPLC indicated complete conversion to the 5-N-oxide intermediate. The reaction mixture was again cooled in an ice water bath. The reaction mixture was treated with ammonium hydroxide solution (50 mL, 30%) and stirred vigorously. The mixture was treated with p-toluenesulfonyl chloride (5.24 g, 27.5 mmol) and allowed to come to ambient temperature. After 30 min, the reaction was diluted with 50 mL of water, and the phases were separated. The organic portion was washed with water (75 mL), brine (75 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to yield a light brown solid. The solid was purified by chromatography (SiO2, 95:5 CHCl3:MeOH) and then recrystallized from acetonitrile to give 4.52 g of 7-bromo-N1-isopropyl-2-propyl-1H-imidazo[4,5-c]quinoline-1,4-diamine as off white crystals. mp 226–228° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.44 (d, J=8.7 Hz, 1H), 7.71 (d, J=2.1 Hz, 1H), 7.36 (dd, J=8.7, 2.1 Hz, 1H), 6.99 (d, J=1.7 Hz, 1H), 6.73 (s, 2H), 3.53–3.40 (m, 1H), 2.90 (s, 2H), 1.93–1.80 (m, 2H), 1.05–1.00 (m, 9H); 13C NMR (125 MHz, DMSO-d6) δ 154.9, 152.9, 146.3, 132.5, 127.8, 124.2, 123.5, 123.1, 119.7, 114.0, 79.5, 51.4, 28.2, 21.1, 20.6, 14.3; MS (APCI) m/z 362, 364 (M+H)+; Anal. Calcd for C16H20BrN5.0.25H2O: C, 52.40; H, 5.63; N, 19.09; Found: C, 52.03; H, 5.42; N, 19.14.

Workup

  1. temperaturecooled in an ice water bath
  2. customto slowly come to ambient temperature
  3. temperatureThe reaction mixture was again cooled in an ice water bath
  4. customto come to ambient temperature
  5. waitAfter 30 min
  6. customthe phases were separated
  7. washThe organic portion was washed with water (75 mL), brine (75 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto yield a light brown solid
  12. customThe solid was purified by chromatography (SiO2, 95:5 CHCl3:MeOH)
  13. customrecrystallized from acetonitrile

Sources & evidence

ORD record
ord-ac94286a95b149848b950a84f23e611f
Source dataset
uspto-grants-2007_01
Patent number
US07163947B2

Reaction notes

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