Hexamethyldisilazane → 6-amino-3-(2-fluorobenzyl)pyrimidine-2,4(1H,3H)-dione

HRID 858035Notes

Reaction equation

HRID 858035 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([OH:8])[N:5]=[C:4]([OH:9])[N:3]=1.C[Si](N[Si](C)(C)C)(C)C.[F:19][C:20]1[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=1[CH2:22]Br.S([O-])([O-])(=O)=S.[Na+].[Na+].C(=O)(O)[O-].[Na+]>S([O-])([O-])(=O)=O.[NH4+].[NH4+].II.C1(C)C=CC=CC=1>[NH2:1][C:2]1[NH:3][C:4](=[O:9])[N:5]([CH2:22][C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=2[F:19])[C:6](=[O:8])[CH:7]=1

Participants

9

Reactant 5

HCID 13838HexamethyldisilazaneHCID 24477Sodium ThiosulfateHCID 67968alpha-Bromo-o-fluorotolueneHCID 516892Sodium BicarbonateHCID 178507954HCID 178507954, compound

Product 1

HCID 454973636-amino-3-(2-fluorobenzyl)pyrimidine-2,4(1H,3H)-dioneYield 111.9%

Reagents, catalysts & solvents 3

HCID 807IodineCatalystHCID 6097028Ammonium SulfateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 4-amino-2,6-dihydroxypyrimidine (10 g, 79.0 mmol), ammonium sulfate (570 mg, 3.95 mmol), and hexamethyldisilizane (60 mL, 292.3 mmol) was heated to reflux for 3.25 h. At this time, the reaction was cooled to 25° C. and concentrated in vacuo to afford a white solid. The solid was mixed with toluene (12 mL) under argon and then treated with 2-fluorobenzyl bromide (12.6 mL, 102.7 mmol) and iodine (470 mg, 1.58 mmol). This mixture was heated to reflux for 2 h. A brown suspension was formed. The reaction was stirred at 25° C. overnight. At this time, the reaction mixture was cooled to 0° C. and then treated with a solution of sodium thiosulfate (2.47 g in 40 mL of water). A very thick suspension formed which needed to be stirred by hand. The solids were broken up with a spatula. The mixture was then treated with a saturated aqueous sodium bicarbonate solution (300 mL) and was stirred at 0° C. for 30 min. The resulting solid was collected by filtration and washed well with water, toluene, and then ether. The solid was then dried in vacuo to afford 6-amino-3-(2-fluoro-benzyl)-1H-pyrimidine-2,4-dione (20.80 g, quant.) as a tan solid; LRMS for C11H10FN3O2S(M+H)+ at m/z=236.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 3.25 h
  3. concentrationconcentrated in vacuo
  4. customto afford a white solid
  5. temperatureThis mixture was heated
  6. temperatureto reflux for 2 h
  7. customA brown suspension was formed
  8. temperatureAt this time, the reaction mixture was cooled to 0° C.
  9. customA very thick suspension formed which
  10. stirringto be stirred by hand
  11. stirringwas stirred at 0° C. for 30 min
  12. filtrationThe resulting solid was collected by filtration
  13. washwashed well with water, toluene
  14. customThe solid was then dried in vacuo

Sources & evidence

ORD record
ord-ab639ab68f654621ab09a947c224d120
Source dataset
uspto-grants-2006_12
Patent number
US07148229B2

Reaction notes

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