Cesium carbonate → 6-{4-[5-(4-chloro-3-trifluoromethyl-phenylamino)-4H-[1,2,4]triazol-3-yl]phenoxy}-pyrimidine-2,4-diamine

HRID 1994007Notes

Reaction equation

HRID 1994007 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[NH:10][C:11]([C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=3)=[N:12][N:13]=2)=[CH:4][C:3]=1[C:21]([F:24])([F:23])[F:22].C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:32]1([NH2:39])[CH:37]=[CH:36][N:35]=[C:34]([NH2:38])[NH:33]1>O1CCOCC1.CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[NH:10][C:11]([C:14]3[CH:15]=[CH:16][C:17]([O:20][C:36]4[N:35]=[C:34]([NH2:38])[N:33]=[C:32]([NH2:39])[CH:37]=4)=[CH:18][CH:19]=3)=[N:12][N:13]=2)=[CH:4][C:3]=1[C:21]([F:22])([F:23])[F:24]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 1785084084-Chloro-2,4-diaminopyrimidineHCID 178515915HCID 178515915, compound

Product 1

HCID 1785079266-{4-[5-(4-chloro-3-trifluoromethyl-phenylamino)-4H-[1,2,4]triazol-3-yl]phenoxy}-pyrimidine-2,4-diamineYield 46.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

4-[5-(4-chloro-3-trifluoromethyl-phenylamino)-4H[1,2,4]triazol-3-yl]-phenol (1.3 g, 3.66 mmol) was dissolved in 18 mL of anhydrous dioxane in a 10-20 mL microwave vial (Personal Chemistry). Solid Cs2CO3 (1.19 g, 3.66 mmol, 1.0 eq) was added and the reaction mixture was stirred with heating at 80° C. for 10 min, then 4-chloro-2,4-diaminopyrimidine (0.530 g, 3.66 mmol) was added. The vial was capped and microwaved at 200° C. for 25 min. Then the reaction mixture was diluted with ca. 10 mL of MeOH, transferred into a round-bottom flask and concentrated in vacuo to ca. 20 mL. The resulting reddish solution was loaded on a short pad of silica gel and eluted first with 100% ethyl acetate to remove the unreacted starting material and then with 20% MeOH in EtOAc to elute the product. The product was further purified by ISCO system (80 g pre-packed column, 40 min method, 0% to 10% MeOH gradient in ethyl acetate). Solvent was removed in vacuo to give the title product as an off-white solid (0.785 g). Yield 46.3%.

Workup

  1. customThe vial was capped
  2. custommicrowaved at 200° C. for 25 min
  3. customtransferred into a round-bottom flask
  4. concentrationconcentrated in vacuo to ca. 20 mL
  5. washeluted first with 100% ethyl acetate
  6. customto remove the
  7. washwith 20% MeOH in EtOAc to elute the product
  8. customThe product was further purified by ISCO system (80 g pre-packed column, 40 min method, 0% to 10% MeOH gradient in ethyl acetate)
  9. customSolvent was removed in vacuo

Sources & evidence

ORD record
ord-146e614db04f463986617dbeae60b1cb
Source dataset
uspto-grants-2010_01
Patent number
US07652051B2

Reaction notes

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