Benzyl mercaptan → 3-(Benzylthio)-8-chloro-1,7-naphthyridine

HRID 1473492Notes

Reaction equation

HRID 1473492 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[N:7][C:6]=2[Cl:12].CCN(C(C)C)C(C)C.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.[CH2:64]([SH:71])[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=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.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:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[N:7][C:6]=2[Cl:12])[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1

Participants

7

Reactant 4

HCID 7509Benzyl mercaptanHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 722135923-Bromo-8-chloro-1,7-naphthyridine

Product 1

HCID 866875473-(Benzylthio)-8-chloro-1,7-naphthyridineYield 51.4%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
40 °C

Procedure

To a vial charged with 3-bromo-8-chloro-1,7-naphthyridine (Anichem, North Brunswick, N.J.) (360 mg, 1.479 mmol) was added dioxane (5914 μl), DIEA (516 μl, 2.96 mmol), Xantphos (171 mg, 0.296 mmol), Pd2(dba)3 (135 mg, 0.148 mmol) and benzyl mercaptan (184 μl, 1.552 mmol). The vessel was sealed and heated to 40° C. overnight. The mixture was cooled to RT, filtered through diatomaceous earth and dried under reduced pressure. The crude residue was purified with a 25 g silicycle HP column (25 μm spherical silica) ramping EtOAc in heptane (0 to 100%, 10% DCM throughout) to provide 3-(benzylthio)-8-chloro-1,7-naphthyridine (0.218 g, 0.760 mmol, 51.4% yield) as a light yellow solid. m/z (ESI) 287.1 (M+H)+.

Workup

  1. customThe vessel was sealed
  2. temperatureThe mixture was cooled to RT
  3. filtrationfiltered through diatomaceous earth
  4. customdried under reduced pressure
  5. customThe crude residue was purified with a 25 g silicycle HP column (25 μm spherical silica)

Sources & evidence

ORD record
ord-7fda61ab3e1c4552887a8dbc746bba69
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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