Hexamethyldisilazane → HCID 178481264, compound

HRID 231630Notes

Reaction equation

HRID 231630 reaction equation
[CH3:1][N:2]1[C:10]2[N:9]=[C:8]3[N:11]([CH2:17][C:18]4[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=4)[C:12](=[O:16])[CH:13]=[C:14]([OH:15])[N:7]3[C:6]=2[C:5](=[O:25])[N:4]([CH3:26])[C:3]1=O.S([O-])([O-])(=O)=O.[NH4+].[NH4+].C[Si](C)(C)N[Si](C)(C)C.[BH4-].[Li+]>C(Cl)(Cl)Cl.O1CCOCC1>[CH3:1][N:2]1[C:10]2[N:9]=[C:8]3[N:11]([CH2:17][C:18]4[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=4)[C:12](=[O:16])[CH:13]=[C:14]([OH:15])[N:7]3[C:6]=2[C:5](=[O:25])[N:4]([CH3:26])[CH2:3]1

Participants

7

Reactant 4

HCID 13838Hexamethyldisilazane2×HCID 4148881Lithium borohydrideHCID 6097028Ammonium SulfateHCID 178481348HCID 178481348, compound

Product 1

HCID 178481264HCID 178481264, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Reflux a suspension of 395 g (1.06 moles) of 1,3-dimethyl-9-(4-fluorobenzyl)-6-hydroxy-pyrimido[2,1-f]purine-2,4,8(1H,3H,9H)-trione, 12.32 g of ammonium sulfate and 350 ml of 1,1,1,3,3,3-hexamethyldisilazane in 4 liters of chloroform until a clear solution is obtained (18-24 hr.). Remove chloroform and excess hexamethyldisilazane under reduced pressure, and treat the residual thick gum with 9.6 liters of dry 1,4-dioxan. While stirring the resultant mixture, cautiously add 70.4 g (3.24 moles) of lithium borohydride in portions under a stream of dry nitrogen. When foaming subsides, heat the mixture to 100° C. for 18 hr. or until all starting material has been consumed (as determined by TLC on silica with chloroform(90)-methanol(10)-acetic acid(1)). Remove a portion of the dioxane under reduced pressure, purge the system with nitrogen as the vacuum is released, allow the residue to cool, and add 3 liters of chloroform with stirring. Add 1.3 liters of water cautiously (because of foaming), followed by 2.3 liters of 3N hydrochloric acid. Stir for one hour; then separate the layers. Extract the aqueous phase with two 1.3-liter volumes of chloroform, and dry the combined extracts over anhydrous sodium sulfate. Filter off the drying agent, and remove solvent from the filtrate under reduced pressure. Dissolve the residual tacky solid in 1.5 liters of boiling acetonitrile, add a small amount of decolorizing carbon, reflux for 15 minutes, and filter through a pad of Celite. Chill the filtrate, and collect the resultant crystals. Wash the crystals with cold acetonitrile, and dry them under vacuum at 50° C. to obtain the title compound, mp 214°-232° C.

Workup

  1. temperatureReflux
  2. customis obtained (18-24 hr.)
  3. customor until all starting material has been consumed (as determined by TLC on silica with chloroform(90)-methanol(10)-acetic acid(1))
  4. customRemove a portion of the dioxane under reduced pressure
  5. custompurge the system with nitrogen as the vacuum
  6. temperatureto cool
  7. additionadd 3 liters of chloroform
  8. additionAdd 1.3 liters of water cautiously (because of foaming)
  9. stirringStir for one hour
  10. customthen separate the layers
  11. extractionExtract the aqueous phase with two 1.3-liter volumes of chloroform
  12. dry with materialdry the combined extracts over anhydrous sodium sulfate
  13. filtrationFilter off the drying agent
  14. customremove solvent from the filtrate under reduced pressure
  15. dissolutionDissolve the residual tacky solid in 1.5 liters of boiling acetonitrile
  16. additionadd a small amount of decolorizing carbon
  17. temperaturereflux for 15 minutes
  18. filtrationfilter through a pad of Celite
  19. temperatureChill the filtrate
  20. customcollect the resultant crystals
  21. washWash the crystals with cold acetonitrile
  22. customdry them under vacuum at 50° C.

Sources & evidence

ORD record
ord-71a3a86564714c63a4d5146c1424a8a4
Source dataset
uspto-grants-1989_07
Patent number
US04847377

Reaction notes

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