Acetone → (7S,8R,9R)-8-Hydroxy-7-methoxy-2-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

HRID 985092Notes

Reaction equation

HRID 985092 reaction equation
[OH:1][C@H:2]1[C:11]2[CH:10]=[CH:9][N:8]3[CH:12]=[C:13]([CH3:15])[N:14]=[C:7]3[C:6]=2[NH:5][C@H:4]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C@H:3]1[OH:22].[C:23]1(C)C=CC(S(O)(=O)=O)=CC=1.CC(C)=O>COC(OC)(C)C>[OH:22][C@H:3]1[C@@H:2]([O:1][CH3:23])[C:11]2[CH:10]=[CH:9][N:8]3[CH:12]=[C:13]([CH3:15])[N:14]=[C:7]3[C:6]=2[NH:5][C@@H:4]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 180AcetoneHCID 6101p-Toluenesulfonic acidHCID 69230549(7S,8R,9R)-7,8-Dihydroxy-2-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

Product 1

HCID 69105999(7S,8R,9R)-8-Hydroxy-7-methoxy-2-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

Reagents, catalysts & solvents 1

HCID 64952,2-DimethoxypropaneSolvent

Conditions

Temperature
25 °C

Procedure

To a suspension of 0.62 g (2.10 mmol) (7S,8R,9R)-7,8-dihydroxy-2-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine in dimethoxypropane is added 0.51 g (26.2 mmol) p-toluenesulphonic acid and acetone (4.0 ml). The mixture is stirred for 6 h at 60° C. and 96 h at 25° C. The reaction is quenched by adding of saturated aqueous sodium hydrogen carbonate solution. 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 (dichloromethane/methanol: 100/3) to give 0.18 g (0.52 mmol/25%) of the title compound as an amorphous solid. 1H-NMR (200 MHz,[D6] DMSO): δ=2.28 (s, 3H), 3.30 (s, 1H), 3.09-4.03 (m, 1H), 4.06 (d, 1H), 4.49 (dd, 1H), 6.67 (d, 1H), 7.22-7.44 (m, 5H), 7.54 (d, 1H), 7.69 (d, 1H).

Workup

  1. customThe reaction is quenched
  2. additionby adding of saturated aqueous sodium hydrogen carbonate solution
  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 (dichloromethane/methanol: 100/3)

Sources & evidence

ORD record
ord-dc04a4b0ef6f4c44af510ad7af05341a
Source dataset
uspto-grants-2005_03
Patent number
US06869949B2

Reaction notes

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