Benzyl mercaptan → HCID 178516457, compound

HRID 1473503Notes

Reaction equation

HRID 1473503 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([OH:12])=[CH:7][CH:8]=[N:9]2)=[CH:4][N:3]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CCN(C(C)C)C(C)C.[CH2:64]([SH:71])[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH2:64]([S:71][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([OH:12])=[CH:7][CH:8]=[N:9]2)=[CH:4][N:3]=1)[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1

Participants

8

Reactant 4

HCID 7509Benzyl mercaptanHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 178516427HCID 178516427, compound

Product 1

HCID 178516457HCID 178516457, compoundYield 22.6%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A screw cap vial was charged with 7-chloro-1,6-naphthyridin-4-ol (0.500 g, 2.77 mmol), Xantphos (0.080 g, 0.138 mmol), tris(dibenzylideneacetone)dipalladium (0.063 g, 0.069 mmol), 1,4-dioxane (5.54 mL) and DIPEA (0.963 mL, 5.54 mmol). The vial was purged with argon, sealed and heated to 80° C. for 10 minutes. The reaction was cooled to room temperature and benzyl mercaptan (0.385 mL, 3.25 mmol) was added and the reaction was continued heating at 80° C. for an additional 30 minutes. The reaction was cooled to room temperature, diluted with water and extracted with DCM (3×). The combined organics were washed with water and brine, dried over magnesium sulfate, filtered and concentrated. The resulting material was concentrated, dissolved in minimal DCM and purified via column chromatography (silica gel 40 g, gradient elution 0 to 50% EtOAc:Heptane) to afford 0.168 g of 7-(benzylthio)-1,6-naphthyridin-4-ol. m/z (ESI) 269.1 (M+H)+.

Workup

  1. customA screw cap vial
  2. customThe vial was purged with argon
  3. customsealed
  4. temperatureThe reaction was cooled to room temperature
  5. temperaturethe reaction was continued heating at 80° C. for an additional 30 minutes
  6. temperatureThe reaction was cooled to room temperature
  7. extractionextracted with DCM (3×)
  8. washThe combined organics were washed with water and brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. concentrationThe resulting material was concentrated
  13. dissolutiondissolved in minimal DCM
  14. custompurified via column chromatography (silica gel 40 g, gradient elution 0 to 50% EtOAc:Heptane)

Sources & evidence

ORD record
ord-c04fc8a797fc4f08a18c94bb70191188
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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