Hydrochloric Acid → 1-[4-amino-2-(2-hydroxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol

HRID 1798875Notes

Reaction equation

HRID 1798875 reaction equation
B(Br)(Br)Br.Br.[NH2:6][C:7]1[C:16]2[N:17]=[C:18]([CH2:25][CH2:26][O:27]C)[N:19]([CH2:20][C:21]([CH3:24])([OH:23])[CH3:22])[C:15]=2[C:14]2[N:13]=[CH:12][CH:11]=[CH:10][C:9]=2[N:8]=1.Cl.[OH-].[Na+]>ClCCl.CO>[NH2:6][C:7]1[C:16]2[N:17]=[C:18]([CH2:25][CH2:26][OH:27])[N:19]([CH2:20][C:21]([CH3:22])([OH:23])[CH3:24])[C:15]=2[C:14]2[N:13]=[CH:12][CH:11]=[CH:10][C:9]=2[N:8]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 25134Boron tribromideHCID 689369541-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol hydrobromide

Product 1

HCID 115946141-[4-amino-2-(2-hydroxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-olYield 29.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of boron tribromide in dichloromethane (22.71 mL of 1 M) was added to a chilled (0° C.) suspension of 1-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol hydrobromide (3.00 g, 7.57 mmol) in dichloromethane (100 mL). The reaction mixture was allowed to come to ambient temperature with stirring for 16 hours. Methanol (30 mL) and hydrochloric acid (30 mL of 6 N) were added and the reaction mixture was heated at reflux for 2.5 hours. The reaction mixture was made basic with sodium hydroxide and the layers were separated. The aqueous layer was extracted with dichloromethane (100 mL). The extract was washed sequentially with water and brine, dried over magnesium sulfate, and then concentrated under reduced pressure to provide a pink solid. This material was crystallized from acetonitrile to provide 0.68 g of 1-[4-amino-2-(2-hydroxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol. The aqueous layer was combined with the water and brine washings and allowed to stand overnight. A precipitate was isolated by filtration, washed with water, and dried under vacuum at 95° C. for 3 hours to provide 1.16 g of 1-[4-amino-2-(2-hydroxyethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol as a pink crystalline solid, mp 194-195° C. Anal. calcd for C15H19N5O2: % C, 59.79; % H, 6.36; % N, 23.24. Found: % C, 59.51; % H, 6.59; % N, 23.34.

Workup

  1. temperaturea chilled
  2. customto come to ambient temperature
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux for 2.5 hours
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with dichloromethane (100 mL)
  7. washThe extract was washed sequentially with water and brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customto provide a pink solid
  11. customThis material was crystallized from acetonitrile

Sources & evidence

ORD record
ord-de970298f3ae453b9722f969c89aa934
Source dataset
uspto-grants-2013_01
Patent number
US08343993B2

Reaction notes

Loading…