Dichloromethane → HCID 57545331, compound

HRID 2383096Notes

Reaction equation

HRID 2383096 reaction equation
[CH3:1][CH:2]([CH3:31])[CH2:3][N:4]1[C:16]2[C:15]3[CH:14]=[CH:13][C:12]([O:17][C:18]4[CH:23]=[CH:22][C:21]([N+:24]([O-])=O)=[CH:20][CH:19]=4)=[CH:11][C:10]=3[N:9]=[C:8]([NH2:27])[C:7]=2[N:6]=[C:5]1[CH2:28][CH2:29][CH3:30].ClCCl.[BH4-].[Na+]>[Ni](Cl)Cl.CO>[NH2:24][C:21]1[CH:22]=[CH:23][C:18]([O:17][C:12]2[CH:13]=[CH:14][C:15]3[C:16]4[N:4]([CH2:3][CH:2]([CH3:31])[CH3:1])[C:5]([CH2:28][CH2:29][CH3:30])=[N:6][C:7]=4[C:8]([NH2:27])=[N:9][C:10]=3[CH:11]=2)=[CH:19][CH:20]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 4311764Sodium borohydrideHCID 67050947HCID 67050947, compound

Product 1

HCID 57545331HCID 57545331, compoundYield 59.7%

Reagents, catalysts & solvents 2

HCID 24385Nickel DichlorideCatalystHCID 887MethanolSolvent

Procedure

Nickel(II)chloride (0.044 g, 0.34 mmol) was added to a solution of 1-(2-methylpropyl)-7-(4-nitrophenoxy)-2-propyl-1H-imidazo[4,5-c]quinolin-4-amine (0.436 g, 1.04 mmol), prepared as described in Example 35, in 20:80 dichloromethane:methanol (30 mL). Sodium borohydride (0.300 g) was added in small portions to the resulting solution, and the reaction was stirred for 25 minutes. A solid formed in the reaction and was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was dissolved in chloroform, and the resulting solution was washed with water. The organic solution was stirred with AMBERLITE IRA-756 ion exchange resin for 30 minutes, and the resin was then removed by filtration. The filtrate was concentrated under reduced pressure to provide a brown oil, which was purified by flash chromatography using a 10 g silica gel cartridge (RediSep, ISCO, 230-400 mesh) attached to a gradient pump system, 254 nm UV detector and fraction collector (ISCO COMBIFLASH Sg100c system). The column was equilibrated with 1% methanol in dichloromethane and the reaction mixture was injected onto the column. The mixture was eluted at 35 mL/minute, with a linear gradient program consisting of 1% methanol/dichloromethane to 5% methanol/dichloromethane over five minutes and holding at 5% methanol/dichloromethane to elute the desired compound. Fractions were examined by TLC and those containing the desired compound were combined and concentrated. The product was then recrystallized from acetonitrile to yield 0.242 g of 7-(4-aminophenoxy)-1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c]quinolin-4-amine as a tan, crystalline solid, mp 190-191° C.

Workup

  1. customprepared
  2. customA solid formed in the reaction
  3. customwas removed by filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. dissolutionThe residue was dissolved in chloroform
  6. washthe resulting solution was washed with water
  7. stirringThe organic solution was stirred with AMBERLITE IRA-756 ion exchange resin for 30 minutes
  8. customthe resin was then removed by filtration
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customto provide a brown oil, which
  11. customwas purified by flash chromatography
  12. washThe mixture was eluted at 35 mL/minute, with a linear gradient program
  13. waitconsisting of 1% methanol/dichloromethane to 5% methanol/dichloromethane over five minutes
  14. washto elute the desired compound
  15. concentrationconcentrated
  16. customThe product was then recrystallized from acetonitrile

Sources & evidence

ORD record
ord-716949b55f2c46999d56ce4cdf53d8f2
Source dataset
uspto-grants-2012_09
Patent number
US08263594B2

Reaction notes

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