Hydrochloric Acid → (8S,9R)-2,3,8-Trimethyl-8-hydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one

HRID 895594Notes

Reaction equation

HRID 895594 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[C:13]3[NH:12][C@H:11]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[C@@H:10]([OH:20])[C:9](=[O:21])[C:8]=3[CH:7]=[CH:6][N:5]2[C:22]=1[CH3:23].[OH-].[Na+].[CH3:26]I.Cl>ClCCl.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:1][C:2]1[N:3]=[C:4]2[C:13]3[NH:12][C@H:11]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[C@:10]([CH3:26])([OH:20])[C:9](=[O:21])[C:8]=3[CH:7]=[CH:6][N:5]2[C:22]=1[CH3:23]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 59943673(8R,9R)-2,3-dimethyl-8-hydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one

Product 1

HCID 69551580(8S,9R)-2,3,8-Trimethyl-8-hydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 6344DichloromethaneSolvent

Procedure

20 g of (8R,9R)-2,3-dimethyl-8-hydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one (WO 98/42707) are dissolved in 100 ml of dichloromethane, and the solution is treated with 4 g of tetrabutylammonium hydrogensulfate, 70 ml of 50% strength aqueous sodium hydroxide solution and with 5 ml of methyl iodide, stirred vigorously at room temperature for 16 h, adjusted to pH 7 using ½ conc. hydrochloric acid with cooling and extracted three times with 100 ml of dichloromethane each time. The organic phases are combined, washed twice with a little water and concentrated to dryness on a rotary evaporator, and the residue obtained is purified twice on silica gel (1st eluent: dichloromethane/methanol 100/3; 2nd eluent: dichloromethane/methanol 100/1). 7.9 g of the title compound are obtained as a yellowish crystallizate of melting point 240° C.

Workup

  1. temperaturewith cooling
  2. extractionextracted three times with 100 ml of dichloromethane each time
  3. washwashed twice with a little water
  4. concentrationconcentrated to dryness on a rotary evaporator
  5. customthe residue obtained
  6. customis purified twice on silica gel (1st eluent: dichloromethane/methanol 100/3; 2nd eluent: dichloromethane/methanol 100/1)

Sources & evidence

ORD record
ord-c64f2b981de64fbea4a9174bf7556c74
Source dataset
uspto-grants-2005_07
Patent number
US06916825B2

Reaction notes

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