Potassium Carbonate → 3-Methoxy-5-(2-phenyl-4-(pyridin-4-yl)thiazol-5-yl)pyridin-2-amine

HRID 538425

Reaction equation

HRID 538425 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1.[CH3:19][O:20][C:21]1[C:22]([NH2:36])=[N:23][CH:24]=[C:25](B2OC(C)(C)C(C)(C)O2)[CH:26]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:19][O:20][C:21]1[C:22]([NH2:36])=[N:23][CH:24]=[C:25]([C:2]2[S:6][C:5]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)=[N:4][C:3]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)[CH:26]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 533980593-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 665905405-Bromo-2-phenyl-4-(pyridin-4-yl)thiazole

Product 1

HCID 591376043-Methoxy-5-(2-phenyl-4-(pyridin-4-yl)thiazol-5-yl)pyridin-2-amine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 5-bromo-2-phenyl-4-(pyridin-4-yl)thiazole (20 mg, 0.062 mmol), 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (39 mg, 0.157 mmol), and aqueous 2.0 M K2CO3 solution (0.5 ml, 1 mmol) in dioxane (0.5 mL) was sparged with Ar. Pd(PPh3)4 (181 mg, 0.157 mmol) was added, the reaction was sealed and irradiated at 120° C. for 15 min. While allowing to cool to rt, the reaction partitioned and the resulting layers were separated. The aqueous phase was extracted with EtOAc (3×) and the combined organic phases were washed with brine, dried (Na2SO4), and concentrated. The resulting residue was purified by reverse phase HPLC to give, after freeze drying, 3-methoxy-5-(2-phenyl-4-(pyridin-4-yl)thiazol-5-yl)pyridin-2-amine as the TFA salt: LCMS (m/z): 361.0 (MH+), tR=0.58 min.

Workup

  1. customwas sparged with Ar
  2. customthe reaction was sealed
  3. customirradiated at 120° C. for 15 min
  4. customthe reaction partitioned
  5. customthe resulting layers were separated
  6. extractionThe aqueous phase was extracted with EtOAc (3×)
  7. washthe combined organic phases were washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customThe resulting residue was purified by reverse phase HPLC
  11. customto give
  12. customafter freeze drying

Sources & evidence

ORD record
ord-b1ec43678c014042ad82e9af5f9403ca
Source dataset
uspto-grants-2014_10
Patent number
US08865732B2

Linked notes

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