Water → HCID 178508965, compound

HRID 2414766Notes

Reaction equation

HRID 2414766 reaction equation
[H-].[Na+].Cl.[NH2:4][C:5]([NH2:7])=[NH:6].C([O:10][C:11](=O)[CH2:12][C:13]([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)=O)C.O>CN(C=O)C>[OH:10][C:11]1[CH:12]=[C:13]([C:15]2[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=2)[N:4]=[C:5]([NH2:7])[N:6]=1

Participants

6

Reactant 4

HCID 962WaterHCID 5742Guanidine HydrochlorideHCID 24758Sodium hydrideHCID 2758844Ethyl 3-(4-Fluorophenyl)-3-Oxopropanoate

Product 1

HCID 178508965HCID 178508965, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Into an oven-dried three neck round bottom, equipped with reflux condenser and nitrogen inlet, and two addition funnels with stoppers, were added oven-activated 5 Å molecular sieves under a stream of dry nitrogen. Sodium hydride (95%) 3.03 grams (0.126 mole) was added to the room temperature flask followed by 40 mL of dry DMF. Stirring was initiated to achieve a suspension of the solids. A solution of guanidine hydrochloride, 11.9 grams (0.125 mole) dissolved in 40 mL of dry DMF was added dropwise via addition funnel over 0.25 hours and stirring was continued for 0.5 hours at room temperature. 3-(4-Fluorophenyl)-3-oxo-propionic ethyl ester, 26.28 grams (0.125 mole) was dissolved in 75 mL of dry DMF and added to the reaction flask via dropper funnel over 0.25 hours. The mixture was then heated at reflux overnight. The mixture was filtered hot and concentrated to afford a heterogeneous mixture. Water, 100 mL, was added and a solid that formed was filtered off and dried. The solid was recrystallized from methanol to afford 4-hydroxy-6-(4-fluorophenyl)pyrimidin-2-amine (51% yield). Hydroxy-pyrimidine compounds were used in the procedure of Method G.

Workup

  1. customInto an oven-dried three neck round bottom
  2. customequipped
  3. temperaturewith reflux condenser and nitrogen inlet
  4. additiontwo addition funnels with stoppers
  5. additionwere added oven-activated 5 Å molecular sieves under a stream of dry nitrogen
  6. additiona suspension of the solids
  7. additionwas added dropwise via addition funnel over 0.25 hours
  8. stirringstirring
  9. additionadded to the reaction flask via dropper funnel over 0.25 hours
  10. temperatureThe mixture was then heated
  11. temperatureat reflux overnight
  12. filtrationThe mixture was filtered hot
  13. concentrationconcentrated
  14. customto afford a heterogeneous mixture
  15. customa solid that formed
  16. filtrationwas filtered off
  17. customdried
  18. customThe solid was recrystallized from methanol

Sources & evidence

ORD record
ord-c59df3f447104ddbb92f5cd6dcb499b5
Source dataset
uspto-grants-2004_11
Patent number
US06815447B2

Reaction notes

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