Hydrogen Sulfide → 2-{6-[3-(Tert-butyl-dimethyl-silanyloxy)-propoxy]-pyridin-3-yl}-4,5,6,7-tetrahydro-benzothiazole

HRID 2424980Notes

Reaction equation

HRID 2424980 reaction equation
[SH2:1].[C:2]([Si:6]([CH3:21])([CH3:20])[O:7][CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][N:13]=1)([CH3:5])([CH3:4])[CH3:3].C(NCC)C.Cl[CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][C:29]1=O>CN(C=O)C.C1(C)C=CC=CC=1.O1CCOCC1>[C:2]([Si:6]([CH3:21])([CH3:20])[O:7][CH2:8][CH2:9][CH2:10][O:11][C:12]1[N:13]=[CH:14][C:15]([C:16]2[S:1][C:28]3[CH2:33][CH2:32][CH2:31][CH2:30][C:29]=3[N:17]=2)=[CH:18][CH:19]=1)([CH3:3])([CH3:5])[CH3:4]

Participants

7

Reactant 4

HCID 402Hydrogen SulfideHCID 8021DiethylamineHCID 132032-ChlorocyclohexanoneHCID 578454316-[3-(Tert-butyl-dimethyl-silanyloxy)-propoxy]-nicotinonitrile

Product 1

HCID 578453912-{6-[3-(Tert-butyl-dimethyl-silanyloxy)-propoxy]-pyridin-3-yl}-4,5,6,7-tetrahydro-benzothiazoleYield 18%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21840791Dioxane tolueneSolvent

Conditions

Temperature
60 °C

Procedure

H2S gas was passed slowly through a solution of 6-[3-(tert-butyl-dimethyl-silanyloxy)-propoxy]-nicotinonitrile (Example 76, 1.14 g, 3.90 mmol) in DMF (25.0 mL) at rt for 30 minutes. Diethylamine (0.60 mL, 5.85 mmol) was added in one portion, and the resultant light green solution was heated at 60° C. for 4 h. The reaction mixture was purged with a stream of argon, and concentrated under reduced pressure. The crude product was filtered through a short pad of silica gel and eluted with EtOAc. The solvent was removed under reduced pressure. The residue was treated with a solution of 2-chlorocyclohexanone (0.244 g, 1.80 mmol) in 10 mL 1:1 toluene/dioxane. The flask was connected to a Dean-Stark apparatus and heated at 150° C. for 18 h. The reaction mixture was concentrated under reduced pressure, the residue washed with water, and extracted with ethyl acetate. The combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel flash chromatography (15% EtOAc in hexanes) to give the title compound (0.29 g, 18%). 1H NMR (400 MHz, CDCl3) δ 8.58 (dd, 1H), 8.02 (dd, 1H), 6.65 (dd, 1H), 4.36 (t, 2H), 3.75 (t, 2H), 2.70-2.82 (m, 4H), 1.90-1.98 (m, 2H), 1.80-1.90 (m, 4H), 0.82 (s, 9H), 0.02 (s, 6H).

Workup

  1. customThe reaction mixture was purged with a stream of argon
  2. concentrationconcentrated under reduced pressure
  3. filtrationThe crude product was filtered through a short pad of silica gel
  4. washeluted with EtOAc
  5. customThe solvent was removed under reduced pressure
  6. temperatureheated at 150° C. for 18 h
  7. concentrationThe reaction mixture was concentrated under reduced pressure
  8. washthe residue washed with water
  9. extractionextracted with ethyl acetate
  10. dry with materialThe combined organic extracts were dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe crude material was purified by silica gel flash chromatography (15% EtOAc in hexanes)

Sources & evidence

ORD record
ord-625a578c30fc4e4dab6a8a6c23e5c074
Source dataset
uspto-grants-2011_06
Patent number
US07964622B2

Reaction notes

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