Potassium Iodide → [4-amino-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-2-yl]methanol

HRID 81928Notes

Reaction equation

HRID 81928 reaction equation
[C:1]([O-:4])(=O)[CH3:2].[K+].[I-].[K+].ClCC1[N:11]([CH2:24][CH:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[C:12]2[C:21]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[N:15]=[C:14]([NH2:22])[C:13]=2[N:23]=1.O.[OH-].[Li+]>O>[NH2:22][C:14]1[C:13]2[N:23]=[C:2]([CH2:1][OH:4])[N:11]([CH2:24][CH:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[C:12]=2[C:21]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[N:15]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 168937Lithium hydroxide, monohydrateHCID 517044Potassium AcetateHCID 67262961HCID 67262961, compound

Product 1

HCID 57555858[4-amino-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-2-yl]methanolYield 38.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

Potassium acetate (0.41 g, 4.16 mmol) and potassium iodide (0.28 g, 1.66 mmol) were added to a stirring solution of 2-(chloromethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.55 g, 1.66 mmol) and the resulting suspension was heated to 50° C. After 17 hours, the suspension was cooled to ambient temperature and concentrated under reduced pressure. The residue was suspended in methanol (10 mL) and water (5 mL) and lithium hydroxide monohydrate (0.35 g, 8.31 mmol) was added in one portion. The resulting solution was stirred at ambient temperature 18 hours and concentrated under reduced pressure. The residue was diluted with water (20 mL) and neutralized with hydrochloric acid (6 N in water). The aqueous layer was extracted with dichloromethane (2×50 mL) and ethyl acetate (50 mL). The combined organic fractions were concentrated to a yellow solid which was crystallized from acetonitrile. The crystals were isolated by filtration and dried in a vacuum oven at 65° C. to provide 0.20 g of [4-amino-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-2-yl]methanol as an off-white solid, mp 239-241° C.

Workup

  1. temperaturethe suspension was cooled to ambient temperature
  2. concentrationconcentrated under reduced pressure
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue was diluted with water (20 mL)
  5. extractionThe aqueous layer was extracted with dichloromethane (2×50 mL) and ethyl acetate (50 mL)
  6. concentrationThe combined organic fractions were concentrated to a yellow solid which
  7. customwas crystallized from acetonitrile
  8. customThe crystals were isolated by filtration
  9. customdried in a vacuum oven at 65° C.

Sources & evidence

ORD record
ord-8a3a8fe19fec4f7bbc15a8aa713776c0
Source dataset
uspto-grants-2014_09
Patent number
US08846710B2

Reaction notes

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