Sodium methanethiolate → HCID 70652423, compound

HRID 2409511Notes

Reaction equation

HRID 2409511 reaction equation
FC(OC(=O)C)(F)F.Cl[C:10]1[N:15]=[CH:14][C:13]([CH2:16][C:17]2[C:26]3[CH2:25][CH2:24][CH2:23][CH2:22][C:21]=3[N:20]=[C:19]([C:27]([NH:29][C@H:30]3[CH2:35][CH2:34][CH2:33][CH2:32][C@@H:31]3[OH:36])=[O:28])[CH:18]=2)=[CH:12][CH:11]=1.[CH3:37][S-:38].[Na+]>CS(C)=O.C(OCC)(=O)C>[OH:36][C@H:31]1[CH2:32][CH2:33][CH2:34][CH2:35][C@@H:30]1[NH:29][C:27]([C:19]1[CH:18]=[C:17]([CH2:16][C:13]2[CH:14]=[N:15][C:10]([S:38][CH3:37])=[CH:11][CH:12]=2)[C:26]2[CH2:25][CH2:24][CH2:23][CH2:22][C:21]=2[N:20]=1)=[O:28]

Participants

5

Reactant 2

HCID 4378561Sodium methanethiolate2×HCID 89485440HCID 89485440, compound

Product 1

HCID 70652423HCID 70652423, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-[(6-chloropyridin-3-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]-5,6,7,8-tetrahydroquinoline-2-carboxamide trifluoromethyl acetate (0.060 g, 0.18 mmol) in 1 mL of DMSO was added sodium thiomethoxide (9.8 mg, 0.14 mmol). The mixture was heated at 80° C. for 1 h, at 90° C. for 1 h, then cooled to rt. After 15 h, additional sodium thiomethoxide (9.3 mg, 0.14 mmol) was added and the mixture was heated at 100° C. for 1 h, then cooled to rt. The mixture was diluted with ethyl acetate, washed 2× with water and 1× with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 35-85% ethyl acetate in hexanes, to provide the title compound that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 412.0 for [M+H]+: 1H NMR (400 MHz, d6-DMSO) δ 8.32 (s, 1H), 8.14 (d, J=8.0 Hz, 1H), 7.53 (s, 1H), 5.43-7.40 (m, 1H), 7.25 (d, J=8.2 Hz, 1H), 4.67 (d, J=5.5 Hz, 1H), 4.02 (s, 2H), 3.54-3.48 (m, 1H), 3.43-3.37 (m, 1H), 3.00 (br s, 2H), 2.72 (br s, 2H), 1.91-1.87 (m, 2H), 1.79 (s, 3H), 1.65-1.59 (m, 2H), 1.24-1.17 (m, 3H).

Workup

  1. temperaturecooled to rt
  2. temperaturethe mixture was heated at 100° C. for 1 h
  3. temperaturecooled to rt
  4. washwashed 2× with water and 1× with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified via silica gel chromatography
  9. washeluting with 35-85% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-77d5cb8325464a1c9b601439d2b04ae9
Source dataset
uspto-grants-2014_08
Patent number
US08815902B2

Reaction notes

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