Toluene → 4-(benzyloxy)-N-(4-methylthiazol-2-yl)pyridin-2-amine

HRID 910889Notes

Reaction equation

HRID 910889 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH3:7])[N:6]=1.[CH2:8]([O:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18](Cl)[CH:17]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.O>[CH2:8]([O:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]([NH:1][C:2]2[S:3][CH:4]=[C:5]([CH3:7])[N:6]=2)[CH:17]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 741432-Amino-4-methylthiazoleHCID 534041974-(Benzyloxy)-2-chloropyridine

Product 1

HCID 866347144-(benzyloxy)-N-(4-methylthiazol-2-yl)pyridin-2-amineYield 48%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A 250 mL round-bottomed flask was charged with 2-amino-4-methylthiazole (43.8 mL, 17.5 mmol), 4-(benzyloxy)-2-chloropyridine (4.23 g, 19.3 mmol), potassium phosphate (4.09 g, 19.3 mmol), and toluene (44 mL), and the reaction mixture was degassed with nitrogen. Tris(dibenzylideneacetone)-dipalladium (0) (0.401 g, 0.438 mmol) and 9,9-dimethyl-4,5-bis(diphenyl-phosphino)-xanthene (0.279 g, 0.482 mmol) were added, and the reaction mixture was degassed with nitrogen. The reaction mixture was warmed to 90° C., degassed water (15 mL) was added, and reaction mixture was stirred at 90° C. overnight. Water was added, and the reaction mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and filtered through a small plug of silica gel, and the filtrate was concentrated down to 50 mL of ethyl acetate and filtered to afford 4-(benzyloxy)-N-(4-methylthiazol-2-yl)pyridin-2-amine (2.50 g, 47.5% yield) as a white solid. 1H NMR (CDCl3) δ 9.29 (bs, 1H), 8.15 (d, 1H), 7.39 (m, 4H), 7.35 (m, 1H), 6.53 (dd, 1H), 6.41 (d, 1H), 6.36 (d, 1H), 5.07 (s, 2H), 2.33 (s, 3H). Mass spectrum (esi) m/z=298 (M

Workup

  1. customthe reaction mixture was degassed with nitrogen
  2. customthe reaction mixture was degassed with nitrogen
  3. customdegassed water (15 mL)
  4. additionwas added
  5. customreaction mixture
  6. extractionthe reaction mixture was extracted with ethyl acetate
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. filtrationfiltered through a small plug of silica gel
  9. concentrationthe filtrate was concentrated down to 50 mL of ethyl acetate
  10. filtrationfiltered

Sources & evidence

ORD record
ord-9e1bc0a8e00348de9b492dea08001071
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

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