Sulfuric Acid → (7R,8R,9R)-8-Hydroxy-7-[2-(2-methoxyethoxy)ethoxy]-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

HRID 985082Notes

Reaction equation

HRID 985082 reaction equation
[OH:1][C@@H:2]1[C:11]2[CH:10]=[CH:9][N:8]3[C:12]([CH3:16])=[C:13]([CH3:15])[N:14]=[C:7]3[C:6]=2[NH:5][C@H:4]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:3]1[OH:23].S(=O)(=O)(O)O.C(Cl)Cl.[OH-].[Na+].[CH3:34][O:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40]O>>[OH:23][C@H:3]1[C@H:2]([O:1][CH2:40][CH2:39][O:38][CH2:37][CH2:36][O:35][CH3:34])[C:11]2[CH:10]=[CH:9][N:8]3[C:12]([CH3:16])=[C:13]([CH3:15])[N:14]=[C:7]3[C:6]=2[NH:5][C@@H:4]1[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 5

HCID 1118Sulfuric AcidHCID 6344DichloromethaneHCID 8134Diethylene Glycol Monomethyl EtherHCID 14798Sodium HydroxideHCID 10215014(7R,8R,9R)-2,3-dimethyl-7,8-dihydroxy-9-phenyl-7,8,9,10-tetrahydro-imidazo[1,2-h][1,7]naphthyridine

Product 1

HCID 9909547(7R,8R,9R)-8-Hydroxy-7-[2-(2-methoxyethoxy)ethoxy]-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

Conditions

Temperature
50 °C

Procedure

5 g of (7R,8R,9R)-7,8-dihydroxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]-naphthyridine are dissolved in 40 ml of 2-(2-methoxyethoxy)ethanol, 3.2 g of sulfuric acid (98% strength) are added and the mixture is warmed at 50° C. for 16 hours. It is then poured onto ice, 100 ml of methylene chloride are added and the mixture is adjusted to pH 7 using aqueous 8 N sodium hydroxide solution. After separation of the organic phase, the aqueous phase is extracted a further two times using 50 ml of methylene chloride each time, the combined organic phases are washed with 100 ml of water, dried over sodium sulfate and the solvent is stripped off in vacuo. The residue is purified on silica gel (eluent: diethyl ether/2-propanol=10/1). 105 mg of the title compound are obtained. 1H-NMR (200 MHz, DMSO): δ=2.25 (s, 3H), 2.33 (s, 3H), 3.23 (s, 3H), 3.32-3.47 (m, 6H), 3.59-3.69 (m, 2H), 3.97-4.07 (q, 1H), 4.44-4.47 (m, 2H), 5.18-5.21 (d, 1 OH), 5.85-5.86 (d, 1NH), 6.74-6.78 (d, 1H), 7.19-7.45 (m, 6H).

Workup

  1. additionare added
  2. customAfter separation of the organic phase
  3. extractionthe aqueous phase is extracted a further two times
  4. washthe combined organic phases are washed with 100 ml of water
  5. dry with materialdried over sodium sulfate
  6. customThe residue is purified on silica gel (eluent: diethyl ether/2-propanol=10/1)

Sources & evidence

ORD record
ord-7aa1e6a236aa47eb8a55329e9455a090
Source dataset
uspto-grants-2005_03
Patent number
US06869949B2

Reaction notes

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