Water → 4-(2-(5-Fluoro-6-methoxypyridin-3-ylamino)-5-(2-methylprop-1-enyl)pyridin-3-YL)-6-methyl-1,3,5-triazin-2-amine

HRID 1621984Notes

Reaction equation

HRID 1621984 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:18]2[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([NH2:25])[N:19]=2)[C:5]([NH:8][C:9]2[CH:10]=[N:11][C:12]([O:16][CH3:17])=[C:13]([F:15])[CH:14]=2)=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].O.[CH3:33][C:34]1([CH3:45])[C:38](C)(C)OB(C=C(C)C)O1>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.O1CCOCC1>[F:15][C:13]1[CH:14]=[C:9]([NH:8][C:5]2[C:4]([C:18]3[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([NH2:25])[N:19]=3)=[CH:3][C:2]([CH:33]=[C:34]([CH3:45])[CH3:38])=[CH:7][N:6]=2)[CH:10]=[N:11][C:12]=1[O:16][CH3:17]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 151484474,4,5,5-Tetramethyl-2-(2-methylprop-1-en-1-yl)-1,3,2-dioxaborolaneHCID 685176504-(5-Chloro-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-YL)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 666121544-(2-(5-Fluoro-6-methoxypyridin-3-ylamino)-5-(2-methylprop-1-enyl)pyridin-3-YL)-6-methyl-1,3,5-triazin-2-amineYield 88%

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To 4-(5-chloro-2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.85 g, 2.350 mmol) was added dioxane (23.50 mL), potassium carbonate in water (3.52 mL, 7.05 mmol), 4,4,5,5-tetramethyl-2-(2-methylprop-1-enyl)-1,3,2-dioxaborolane (0.723 mL, 3.52 mmol) (Frontier Scientific), and bis-(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (Aldrich; 0.083 g, 0.117 mmol). The resulting mixture was sparged with nitrogen and then stirred at 80° C. for 16 h. The reaction mixture was subsequently diluted with 150 mL of EtOAc, added to a separatory funnel, partitioned with sodium bicarbonate (saturated, aqueous), washed 2 times with 150 mL of sodium bicarbonate (saturated, aqueous), separated, dried over sodium sulfate, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0% to 100% EtOAc/hexanes) gave the title compound (88% yield) as a yellow solid. m/z (ESI, +ve ion) 382.2 (M+H)+.

Workup

  1. customThe resulting mixture was sparged with nitrogen
  2. additionThe reaction mixture was subsequently diluted with 150 mL of EtOAc
  3. additionadded to a separatory funnel
  4. custompartitioned with sodium bicarbonate (saturated, aqueous)
  5. washwashed 2 times with 150 mL of sodium bicarbonate (saturated, aqueous)
  6. customseparated
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customChromatographic purification of the residue (silica gel, 0% to 100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-b7328863cb4e44ffb07f0c714e686d3b
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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