Cyanogen Bromide → HCID 86626298, compound

HRID 1097591Notes

Reaction equation

HRID 1097591 reaction equation
[Cl:1][C:2]1[C:11]([NH2:12])=[C:10]([NH:13][C@H:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[N:22]#[C:23][Br:24]>C(O)C>[BrH:24].[Cl:1][C:2]1[C:11]2[N:12]=[C:23]([NH2:22])[N:13]([C@H:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH3:15])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1

Participants

4

Reactant 2

HCID 10476Cyanogen Bromide4×HCID 86626300HCID 86626300, compound

Product 1

HCID 86626298HCID 86626298, compoundYield 53.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 2-chloro-N4-[(1S)-1-phenylethyl]quinoline-3,4-diamine (13.0 g, 43.7 mmol) in ethanol (100 mL) was heated to 80° C. for 30 minutes. Cyanogen bromide (4.6 g, 44 mmol) was added, and the dark solution was heated at 80° C. for one hour. An analysis by LC/MS indicated the presence of starting material. Additional cyanogen bromide (4.6 g, 44 mmol) was added, and the reaction was stirred overnight at 80° C. The reaction was still incomplete, and additional cyanogen bromide (4.6 g, 44 mmol) was added. The reaction was heated overnight at 100° C. after a fourth equivalent of cyanogen bromide (4.6 g, 44 mmol) was added. The solvent was removed under reduced pressure, and aqueous sodium hydroxide (200 mL of 2 N) was slowly added to the resulting oil. The mixture was stirred for two hours at room temperature, and a precipitate formed, which was isolated by filtration. The solid was then purified by automated flash chromatography (silica cartridge, eluting with aqueous ammonium hydroxide:methanol:dichloromethane in a gradient from 0:0:100 to 0.3:4.7:95) to provide 9.4 g of 4-chloro-1-[(1S)-1-phenylethyl]-1H-imidazo[4,5-c]quinolin-2-amine hydrobromide as a brown solid. A portion of the product was purified again by automated flash chromatography (silica cartridge, eluting with aqueous ammonium hydroxide:methanol:dichloromethane in a gradient from 0:0:100 to 0.2:3.8:96) to provide a sample of the product as gray needles, mp 170-172° C.

Workup

  1. additionwas added
  2. customThe solvent was removed under reduced pressure, and aqueous sodium hydroxide (200 mL of 2 N)
  3. additionwas slowly added to the resulting oil
  4. stirringThe mixture was stirred for two hours at room temperature
  5. customa precipitate formed
  6. customwhich was isolated by filtration
  7. customThe solid was then purified by automated flash chromatography (silica cartridge
  8. washeluting with aqueous ammonium hydroxide

Sources & evidence

ORD record
ord-0c4f1804af674d7683ee76d2cf932f33
Source dataset
uspto-grants-2012_03
Patent number
US08143270B2

Reaction notes

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