1,4-Dioxane → 3-(Benzylthio)-8-(2-methoxy-4-(trifluoromethyl)phenyl)-1,7-naphthyridine

HRID 1473493Notes

Reaction equation

HRID 1473493 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1B(O)O.[CH2:16]([S:23][C:24]1[CH:25]=[N:26][C:27]2[C:32]([CH:33]=1)=[CH:31][CH:30]=[N:29][C:28]=2Cl)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1NC)(C)(C)C.O>[CH2:16]([S:23][C:24]1[CH:25]=[N:26][C:27]2[C:32]([CH:33]=1)=[CH:31][CH:30]=[N:29][C:28]=2[C:4]1[CH:5]=[CH:6][C:7]([C:9]([F:12])([F:11])[F:10])=[CH:8][C:3]=1[O:2][CH3:1])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acidHCID 866875473-(Benzylthio)-8-chloro-1,7-naphthyridine

Product 1

HCID 866875483-(Benzylthio)-8-(2-methoxy-4-(trifluoromethyl)phenyl)-1,7-naphthyridineYield 91.1%

Reagents, catalysts & solvents 2

HCID 178482226HCID 178482226, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a vial charged with 2-methoxy-4-(trifluoromethyl)phenyl boronic acid (Combi-Blocks, San Diego, Calif.) (0.268 g, 1.216 mmol), 3-(benzylthio)-8-chloro-1,7-naphthyridine (0.218 g, 0.760 mmol), and potassium phosphate tribasic (0.189 ml, 2.280 mmol) was added dioxane (3.05 ml) and water (1.016 ml). The mixture was purged with argon prior to the addition of 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(II) chloride (0.054 g, 0.076 mmol). The vessel was sealed and heated to 60° C. overnight. After cooling to ambient temperature, the mixture was loaded directly onto a silica gel loading column and purified with a 40 g HP spherical column (silicycle) (SiliCycle, Inc. Quebec City, Canada) ramping EtOAc in heptane (0 to 35%, then isocratic at 35%) to provide 3-(benzylthio)-8-(2-methoxy-4-(trifluoromethyl)phenyl)-1,7-naphthyridine (0.295 g, 0.692 mmol, 91% yield) as an off-white foam. m/z (ESI) 427.3 (M+H)+.

Workup

  1. customThe mixture was purged with argon
  2. customThe vessel was sealed
  3. temperatureAfter cooling to ambient temperature
  4. custompurified with a 40 g HP spherical column (silicycle) (SiliCycle, Inc. Quebec City, Canada)

Sources & evidence

ORD record
ord-803a6665c1c84f96943080ff028c4d2c
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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