Potassium Hydroxide → (7R,8R,9R)-3-Chloro-8-hydroxy-7-(2-methoxyethoxy)-2-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

HRID 985088Notes

Reaction equation

HRID 985088 reaction equation
C([N:4]1[C:13]2[C:12]3=[N:14][C:15]([CH3:18])=[C:16]([Cl:17])[N:11]3[CH:10]=[CH:9][C:8]=2[C@@H:7]([O:19][CH2:20][CH2:21][O:22][CH3:23])[C@H:6]([O:24]C(=O)C(C)(C)C)[C@H:5]1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)(=O)C.[OH-].[K+].O.NN>CO>[Cl:17][C:16]1[N:11]2[CH:10]=[CH:9][C:8]3[C@@H:7]([O:19][CH2:20][CH2:21][O:22][CH3:23])[C@H:6]([OH:24])[C@@H:5]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[NH:4][C:13]=3[C:12]2=[N:14][C:15]=1[CH3:18]

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 69586435HCID 69586435, compound

Product 1

HCID 10215970(7R,8R,9R)-3-Chloro-8-hydroxy-7-(2-methoxyethoxy)-2-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of 0.27 g (0.53 mmol) (7R,8R,9R)-10-acetyl-3-chloro-7-(2-methoxyethoxy)-2-methyl-9-phenyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine, 0.10 ml (0.60 mmol) aqueous potassium hydroxide (6 N) and 0.20 ml (5.14 mmol) hydrazine hydrate in methanol is stirred at 60° C. for 4 h. The methanol is removed in vacuo and the reaction mixture is diluted with water. Subsequently the mixture is extracted twice with dichloromethane. The combined organic layers are washed with brine, dried over sodium sulphate and evaporated in vacuo. The crude product is purified by column chromatography (toluene/dioxane/acetic acid: 8/1/1) to provide 0.34 g (0.88 mmol/51%) of the title compound as a colourless solid with a melting point of 123-126° C. (acetone).

Workup

  1. customThe methanol is removed in vacuo
  2. additionthe reaction mixture is diluted with water
  3. extractionSubsequently the mixture is extracted twice with dichloromethane
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over sodium sulphate
  6. customevaporated in vacuo
  7. customThe crude product is purified by column chromatography (toluene/dioxane/acetic acid: 8/1/1)

Sources & evidence

ORD record
ord-b3416889797348e2ae9498801c05eeef
Source dataset
uspto-grants-2005_03
Patent number
US06869949B2

Reaction notes

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