Methanol → Methyl 4-[(2,6-diaminopyrimidin-4-yl)oxy]benzoate

HRID 1994008Notes

Reaction equation

HRID 1994008 reaction equation
[OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.Cl[C:13]1[CH:18]=[C:17]([NH2:19])[N:16]=[C:15]([NH2:20])[N:14]=1.CO>O1CCOCC1.C([O-])([O-])=O.[Cs+].[Cs+]>[NH2:20][C:15]1[N:14]=[C:13]([O:1][C:2]2[CH:3]=[CH:4][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:10][CH:11]=2)[CH:18]=[C:17]([NH2:19])[N:16]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 7456MethylparabenHCID 674322,4-Diamino-6-chloropyrimidine

Product 1

HCID 59135324Methyl 4-[(2,6-diaminopyrimidin-4-yl)oxy]benzoateYield 31.2%

Reagents, catalysts & solvents 2

HCID 10796Cesium carbonateSolventHCID 312751,4-DioxaneSolvent

Procedure

Methyl 4-hydroxybenzoate (1.52 g, 10.0 mmol) was dissolved in 18 mL of anhydrous dioxane in 10-20 mL microwave vial (Personal Chemistry) and solid Cs2CO3 was added to this solution. The suspension was stirred at ambient temperature for 10 min, then 4-chloro-2,6-diaminopyrimidine (1.45 g, 10.0 mmol) was added. The vial was capped and microwaved at 200° C. for 40 min. Then MeOH was added to dissolve the formed suspension to produce a clear amber solution. The solution was transferred into a round-bottom flask and concentrated down to ca. 20 mL. This solution was purified by silica gel chromatography using 100% ethyl acetate as eluent. The product was additionally re-crystallized from ca. 50 mL of 4:1 mixture of EtOAc/MeOH. The product was filtered, washed with 40 mL of EtOAc, 40 mL of anhydrous Et2O and dried in vacuo to give the title product as a white solid (0.812 g). Yield 31.2%.

Workup

  1. additionwas added to this solution
  2. customThe vial was capped
  3. custommicrowaved at 200° C. for 40 min
  4. dissolutionto dissolve the formed suspension
  5. customto produce a clear amber solution
  6. customThe solution was transferred into a round-bottom flask
  7. concentrationconcentrated down to ca. 20 mL
  8. customThis solution was purified by silica gel chromatography
  9. customThe product was additionally re-crystallized from ca. 50 mL of 4:1 mixture of EtOAc/MeOH
  10. filtrationThe product was filtered
  11. washwashed with 40 mL of EtOAc, 40 mL of anhydrous Et2O
  12. customdried in vacuo

Sources & evidence

ORD record
ord-9f79515b268544d7a2aac4230619de9e
Source dataset
uspto-grants-2010_01
Patent number
US07652051B2

Reaction notes

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