Sodium ethanethiolate → HCID 69498201, compound

HRID 418723Notes

Reaction equation

HRID 418723 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([C:12]2[S:20][C:19]3[C:14](=[N:15][CH:16]=[CH:17][C:18]=3[O:21][C:22]3[CH:27]=[CH:26][C:25]([NH:28][C:29](=[O:42])[CH2:30][C:31]([NH:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=4[O:40][CH3:41])=[O:32])=[CH:24][C:23]=3[F:43])[CH:13]=2)[CH:9]=[CH:10][CH:11]=1.[CH2:44]([S-:46])[CH3:45].[Na+].C(OCC)(=[O:50])C.CO.I([O-])(=O)(=O)=O.[Na+]>CN(C=O)C.O>[CH2:44]([S:46]([CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([C:12]2[S:20][C:19]3[C:14](=[N:15][CH:16]=[CH:17][C:18]=3[O:21][C:22]3[CH:27]=[CH:26][C:25]([NH:28][C:29](=[O:42])[CH2:30][C:31]([NH:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=4[O:40][CH3:41])=[O:32])=[CH:24][C:23]=3[F:43])[CH:13]=2)[CH:9]=[CH:10][CH:11]=1)=[O:50])[CH3:45]

Participants

7

Reactant 4

HCID 4459711Sodium ethanethiolateHCID 21584119Ethylacetate methanolHCID 23667635Sodium periodateHCID 58790205HCID 58790205, compound

Product 1

HCID 69498201HCID 69498201, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To chloride 366 (0.048 g, 0.077 mmol) in dry DMF (10 mL) was added sodium ethanethiolate (100 mg, 1.19 mmol) and the mixture was heated to 50° C., for 18 h. It was cooled, partitioned between ethyl acetate and water, washed with brine, dried (MgSO4), filtered, run through a short plug of silica gel, and concentrated. The residue was suspended in 1:1 ethyl acetate/methanol (50 mL) and sodium periodate (0.060 g, 0.28 mmol) in water (5 mL) was added. The reaction mixture was stirred for 6 h, concentrated and the residue was partitioned between ethyl acetate and water. The organic phase was collected, washed with brine, dried (anhydrous MgSO4), filtered, and concentrated. Reverse phase HPLC (Aquasil C-18 column, 60-95% MeOH/H2O+HCO2H, 30 min. linear gradient elution) of the residue followed by lyophilization afforded 368 (0.015 g, 29% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.71 (s, 1H); 9.66 (s, 1H); 8.51 (d, J=5.5, 1H); 8.12 (s, 1H); 8.07 (d, J=8.8, 1H); 7.89 (dd, J=12.9, 2.2, 1H); 7.53-7.41 (m, 5H); 7.09-7.03 (m, 3H); 6.94-6.90 (m, 1H); 6.64 (dd, J=5.5, 0.5, 1H); 4.22 (t, J=6.3, 2H); 3.86 (s, 3H); 3.65 (s, 2H); 2.93-2.65 (m, 4H); 2.13 (quint, J=8.0, 2H); 1.29 (t, J=7.4, 3H). LCMS: (M+H) 662.0.

Workup

  1. temperatureIt was cooled
  2. custompartitioned between ethyl acetate and water
  3. washwashed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionwas added
  8. concentrationconcentrated
  9. customthe residue was partitioned between ethyl acetate and water
  10. customThe organic phase was collected
  11. washwashed with brine
  12. dry with materialdried (anhydrous MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. washReverse phase HPLC (Aquasil C-18 column, 60-95% MeOH/H2O+HCO2H, 30 min. linear gradient elution) of the residue

Sources & evidence

ORD record
ord-ce213bb7e75b464d9212e5aa99c4ba2b
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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