Tetrahydrofuran → 6-[(6-Acetylpyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one

HRID 82449Notes

Reaction equation

HRID 82449 reaction equation
[OH:1][C@@H:2]1[C@@H:7]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[C:12]4[CH:32]=[CH:31][CH:30]=[CH:29][C:13]4=[C:14]([CH2:19][C:20]4[CH:21]=[N:22][C:23]([C:26](C)=[CH2:27])=[CH:24][CH:25]=4)[CH:15]=3)[N:10]=[CH:9]2)[CH2:6][CH2:5][O:4][CH2:3]1.C1C[O:36]CC1.I([O-])(=O)(=O)=O.[Na+]>CC(C)=O.O.O.[Ru](Cl)Cl>[C:26]([C:23]1[N:22]=[CH:21][C:20]([CH2:19][C:14]2[CH:15]=[C:16]3[C:11](=[C:12]4[CH:32]=[CH:31][CH:30]=[CH:29][C:13]=24)[N:10]=[CH:9][N:8]([C@H:7]2[CH2:6][CH2:5][O:4][CH2:3][C@@H:2]2[OH:1])[C:17]3=[O:18])=[CH:25][CH:24]=1)(=[O:36])[CH3:27]

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 23667635Sodium periodateHCID 679699843-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-6-[(6-isopropenylpyridin-3-yl)methyl]benzo[h]quinazolin-4(3H)-one

Product 1

HCID 510007046-[(6-Acetylpyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one

Reagents, catalysts & solvents 3

HCID 19904977Ruthenium chloride hydroxide (RuCl2(OH))CatalystHCID 180AcetoneSolventHCID 962WaterSolvent2×

Procedure

To a solution of 3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-6-[(6-isopropenylpyridin-3-yl)methyl]benzo[h]quinazolin-4(3H)-one (0.042 g, 0.098 mmol) in a mixture of 1 mL of acetone, 1 mL of THF, and 1 mL of water was added ruthenium(II) chloride hydrate (5.5 mg, 0.025 mmol) and sodium periodate (0.084 g, 0.39 mmol). After 1.5 h, the mixture was diluted with water and extracted 3× with dichloromethane. The combined organic fractions were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-5% methanol in dichloromethane to provide the title compound that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 460.1763 for [M+H]+ [Calc'd for C25H24N3O4, [M+H]+=430.1761]: 1H NMR (400 MHz, CDCl3) δ 8.89 (d, J=8.1 Hz, 1H), 8.52 (s, 1H), 8.28 (s, 1H), 7.83 (d, J=8.1 Hz, 1H), 7.78 (s, 1H), 7.71 (d, J=8.4 Hz, 1H), 7.65-7.56 (m, 2H), 7.47-7.45 (m, 1H), 4.84-4.78 (m, 1H), 4.33 (s, 2H), 4.26-4.09 (m, 2H), 4.07-4.05 (m, 1H), 3.70 (br s, 1H), 3.57 (t, J=11.0 Hz, 1H), 3.34 (t, J=10.0 Hz, 1H), 2.64 (s, 3H), 2.25-2.20 (m, 1H), 2.01-1.97 (m, 1H).

Workup

  1. extractionextracted 3× with dichloromethane
  2. dry with materialThe combined organic fractions were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified via silica gel chromatography
  6. washeluting with 0-5% methanol in dichloromethane

Sources & evidence

ORD record
ord-24ec1d441535477ab586287496c27460
Source dataset
uspto-grants-2014_09
Patent number
US08846702B2

Reaction notes

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