4-Methyl-3-methylsulfonyl-5-phenyl-4H-1,2,4-triazole → 4-(2-(4-(4-methyl-5-phenyl-4H-1,2,4-triazol-3-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-amine

HRID 252636Notes

Reaction equation

HRID 252636 reaction equation
[NH2:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[C:12]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[N:14]=3)=[CH:11][CH:10]=[CH:9][N:8]=2)=[CH:4][CH:3]=1.[CH3:22][N:23]1[C:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[N:26][N:25]=[C:24]1S(C)(=O)=O.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[CH3:22][N:23]1[C:27]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[N:26][N:25]=[C:24]1[NH:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[C:12]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[N:14]=3)=[CH:11][CH:10]=[CH:9][N:8]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 1640134-Methyl-3-methylsulfonyl-5-phenyl-4H-1,2,4-triazoleHCID 2733832Lithium HexamethyldisilazideHCID 577562184-(2-(4-Aminophenoxy)pyridin-3-yl)pyrimidin-2-amine

Product 1

HCID 589669694-(2-(4-(4-methyl-5-phenyl-4H-1,2,4-triazol-3-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

To a slurry of 4-(2-(4-aminophenoxy)pyridin-3-yl)pyrimidin-2-amine (0.150 g, 0.54 mmol) and 4-methyl-3-(methylsulfonyl)-5-phenyl-4H-1,2,4-triazole (0.14 g, 0.59 mmol) in 0.6 mL THF was added lithium bis(trimethylsilyl) amide, 1.0 m solution in tetrahydrofuran (1.1 ml, 1.1 mmol). The reaction became a solid, and was sealed and heated to 70° C., at which point it became a heterogeneous brown mixture that could be stirred. After 2 h, the reaction did not appear to make further progress. The reaction was quenched with sat'd aqueous NH4Cl and partitioned between DCM and water. The aqueous layer was extracted 1×DCM. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The material was absorbed onto silica gel from MeOH/DCM and dried. The residue was purified by silica gel chromatography, 40 g (0-100% 90/10 DCM/MeOH in MC) to give 4-(2-(4-(4-methyl-5-phenyl-4H-1,2,4-triazol-3-ylamino)phenoxy)pyridin-3-yl)pyrimidin-2-amine as a white solid. MS m/z=437 [M+H]+. Calc'd for C24H20N8O: 436.5.

Workup

  1. customwas sealed
  2. customThe reaction was quenched with sat'd aqueous NH4Cl
  3. custompartitioned between DCM and water
  4. extractionThe aqueous layer was extracted 1×DCM
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe material was absorbed onto silica gel from MeOH/DCM
  9. customdried
  10. customThe residue was purified by silica gel chromatography, 40 g (0-100% 90/10 DCM/MeOH in MC)

Sources & evidence

ORD record
ord-de01b3e3002c4a4fb5bdba3301220f35
Source dataset
uspto-grants-2011_01
Patent number
US07868177B2

Reaction notes

Loading…