Boron tribromide → {4-amino-1-[2,2-dimethyl-3-(methylsulfonyl)propyl]-1H-imidazo[4,5-c]quinolin-2-yl}methanol

HRID 81918Notes

Reaction equation

HRID 81918 reaction equation
[CH3:1][C:2]([CH3:27])([CH2:22][S:23]([CH3:26])(=[O:25])=[O:24])[CH2:3][N:4]1[C:16]2[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[C:8]([NH2:17])[C:7]=2[N:6]=[C:5]1[CH2:18][O:19]CC.B(Br)(Br)Br>ClCCl>[NH2:17][C:8]1[C:7]2[N:6]=[C:5]([CH2:18][OH:19])[N:4]([CH2:3][C:2]([CH3:27])([CH3:1])[CH2:22][S:23]([CH3:26])(=[O:25])=[O:24])[C:16]=2[C:15]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[N:9]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 66700247HCID 66700247, compound

Product 1

HCID 57555846{4-amino-1-[2,2-dimethyl-3-(methylsulfonyl)propyl]-1H-imidazo[4,5-c]quinolin-2-yl}methanolYield 40.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 1-[2,2-dimethyl-3-(methylsulfonyl)propyl]-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.4 g, 1.02 mmol) in dichloromethane (5 mL) was added boron tribromide (5.1 mL, 1M solution in dichloromethane). An exotherm was observed upon addition and the mixture turned light purple. After stirring at ambient temperature for 20 hours, the remaining starting material was consumed by adding boron tribromide (2.5 mL, 1M solution in dichloromethane). The reaction was quenched with aqueous hydrochloric acid (1N, 20 mL) to afford a homogeneous mixture. The layers were separated and the aqueous layer washed with dichloromethane (20 mL). The pH of the aqueous layer was adjusted to 12 by addition of aqueous sodium hydroxide (50%) at which time a solid precipitated out of solution. The solid was stirred for 18 hours, collected by filtration and washed with water. The crude product was purified by chromatography over silica gel (eluting with CMA) to afford a white powder. The powder was triturated with methanol (20 mL). The resulting solid was isolated by filtration, washed with methanol and dried for 4 hours at 65° C. to provide 150 mg of {4-amino-1-[2,2-dimethyl-3-(methylsulfonyl)propyl]-1H-imidazo[4,5-c]quinolin-2-yl}methanol as a white powder, mp 230-232° C.

Workup

  1. additionAn exotherm was observed upon addition
  2. customwas consumed
  3. additionby adding boron tribromide (2.5 mL, 1M solution in dichloromethane)
  4. customThe reaction was quenched with aqueous hydrochloric acid (1N, 20 mL)
  5. customto afford a homogeneous mixture
  6. customThe layers were separated
  7. washthe aqueous layer washed with dichloromethane (20 mL)
  8. additionThe pH of the aqueous layer was adjusted to 12 by addition of aqueous sodium hydroxide (50%) at which time a solid
  9. customprecipitated out of solution
  10. stirringThe solid was stirred for 18 hours
  11. filtrationcollected by filtration
  12. washwashed with water
  13. customThe crude product was purified by chromatography over silica gel (eluting with CMA)
  14. customto afford a white powder
  15. customThe powder was triturated with methanol (20 mL)
  16. customThe resulting solid was isolated by filtration
  17. washwashed with methanol
  18. customdried for 4 hours at 65° C.

Sources & evidence

ORD record
ord-73bebd73d701410bbd19504ff3881df2
Source dataset
uspto-grants-2014_09
Patent number
US08846710B2

Reaction notes

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