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

HRID 82462Notes

Reaction equation

HRID 82462 reaction equation
[H-].[Na+].[CH2:3]([OH:5])[CH3:4].F[C:7]1[N:12]=[CH:11][C:10]([CH2:13][C:14]2[CH:15]=[C:16]3[C:21](=[C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=24)[N:20]=[CH:19][N:18]([C@H:28]2[CH2:33][CH2:32][O:31][CH2:30][C@@H:29]2[OH:34])[C:17]3=[O:35])=[CH:9][CH:8]=1>CS(C)=O.C(OCC)(=O)C>[CH2:3]([O:5][C:7]1[N:12]=[CH:11][C:10]([CH2:13][C:14]2[CH:15]=[C:16]3[C:21](=[C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=24)[N:20]=[CH:19][N:18]([C@H:28]2[CH2:33][CH2:32][O:31][CH2:30][C@@H:29]2[OH:34])[C:17]3=[O:35])=[CH:9][CH:8]=1)[CH3:4]

Participants

6

Reactant 3

HCID 702EthanolHCID 24758Sodium hydrideHCID 67969952HCID 67969952, compound

Product 1

HCID 680503776-[(6-Ethyoxypyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of sodium hydride (0.012 g, 0.31 mmol) in 1 mL of DMSO was added ethanol (0.022 mL, 0.37 mmol). After 5 min, 6-[(6-Fluoropyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one (0.050 g, 0.12 mmol) was added. After 4 h, the reaction was diluted with ethyl acetate, washed with water, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 25-75% ethyl acetate in hexanes to provide the title compound that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 432.1916 for [M+H]+ [Calc'd for C25H26N3O4, [M+H]+=432.1918]: 1H NMR (400 MHz, CDCl3) δ 8.92-8.89 (m, 1H), 8.26 (s, 1H), 8.00 (s, 1H), 7.89-7.86 (m, 1H), 7.84 (s, 1H), 7.65-7.58 (m, 2H), 7.29 (s, 1H), 6.55 (s, 1H), 4.86-4.79 (m, 1H), 4.29-4.06 (m, 7H), 3.59-3.52 (m, 1H), 3.33-3.29 (m, 1H), 3.16 (d, J=6.5 Hz, 1H), 2.29-2.19 (m, 1H), 2.01-1.97 (m, 1H), 1.30-1.27 (m, 1H).

Workup

  1. waitAfter 4 h
  2. washwashed with water
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified via silica gel chromatography
  7. washeluting with 25-75% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-b77a97d37ee145af8009743789c804c4
Source dataset
uspto-grants-2014_09
Patent number
US08846702B2

Reaction notes

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