Sodium methanethiolate → HCID 71471664, compound

HRID 925612Notes

Reaction equation

HRID 925612 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:10]=[C:11]3[C:16](=[C:17]4[N:22]([CH3:23])[CH2:21][CH:20]=[CH:19][C:18]=24)[N:15]=[CH:14][N:13]([C@H:24]2[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]2[OH:30])[C:12]3=[O:31])=[CH:4][CH:3]=1.[CH3:32][S-:33].[Na+]>CS(C)=O.C(OCC)(=O)C>[OH:30][C@H:25]1[CH2:26][CH2:27][CH2:28][CH2:29][C@@H:24]1[N:13]1[C:12](=[O:31])[C:11]2[C:16](=[C:17]3[N:22]([CH3:23])[CH2:21][CH:20]=[CH:19][C:18]3=[C:9]([CH2:8][C:5]3[C:6]([S:33][CH3:32])=[N:7][CH:2]=[CH:3][CH:4]=3)[CH:10]=2)[N:15]=[CH:14]1

Participants

5

Reactant 2

HCID 4378561Sodium methanethiolateHCID 71472666HCID 71472666, compound

Product 1

HCID 71471664HCID 71471664, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-9,10-dihydropyrido[3,2-h]quinazolin-4(3H)-one (Example 1, 0.050 g, 0.11 mmol) in 2 mL of DMSO was added sodium thiomethoxide (0.024 g, 0.34 mol). The mixture was heated in a sealed tube at 100° C. for 15 h, cooled to room temperature, and diluted with ethyl acetate. The organic solution was washed with saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-5% methanol in dichloromethane, and again via preparative reverse phase HPLC to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 448.9 for [M+H]+: 1H NMR (400 MHz, CD3OD) δ 9.05 (br s, 1H), 8.86 (br s, 1H), 8.41 (br s, 1H), 8.02 (s, 1H), 7.86 (br s, 1H), 7.76 (d, J=8.2 Hz, 1H), 7.43 (d, J=8.5 Hz, 1H), 4.80 (s, 2H), 4.56 (s, 2H), 4.22 (br s, 1H), 3.13 (s, 3H), 2.61 (s, 3H), 2.11 (br s, 1H), 1.87-1.72 (m, 5H), 1.48-1.39 (m, 3H).

Workup

  1. temperaturecooled to room temperature
  2. washThe organic solution was washed with saturated aqueous sodium bicarbonate and brine
  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 0-5% methanol in dichloromethane

Sources & evidence

ORD record
ord-dfeb365626b842b695a3276750bdb20f
Source dataset
uspto-grants-2016_03
Patent number
US09284312B2

Reaction notes

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