1-(2-Fluoro-6-(trifluoromethyl)benzyl)-6-methylpyrimidine-2,4(1H,3H)-dione Chemical Properties

Density 

1.413±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

pka

9.49±0.40(Predicted)

Appearance

White to off-white Solid

InChI

InChI=1S/C13H10F4N2O2/c1-7-5-11(20)18-12(21)19(7)6-8-9(13(15,16)17)3-2-4-10(8)14/h2-5H,6H2,1H3,(H,18,20,21)

InChIKey

IJRKKZXPXBTHER-UHFFFAOYSA-N

SMILES

C1(=O)N(CC2=C(C(F)(F)F)C=CC=C2F)C(C)=CC(=O)N1

1-(2-Fluoro-6-(trifluoromethyl)benzyl)-6-methylpyrimidine-2,4(1H,3H)-dione Usage And Synthesis

Uses

1-(2-Fluoro-6-(trifluoromethyl)benzyl)-6-methylpyrimidine-2,4(1H,3H)-dione is a pharmaceutical intermediate ingredient used in the preparation of Elagolix sodium, which is FDA-approved for the treatment of pain associated with moderate to severe pain associated with endometriosis.

Synthesis

Using 1-(2-fluoro-6-(trifluoromethyl)benzyl)urea (2.568 g, 10.9 mmol) and tert-butyl acetoacetate (5.0 g) in toluene (125 mL), the mixture was briefly heated to reflux using a Dean-Stark splitter. Subsequently, tert-butyl acetoacetate (5.0 g) was added and heating to reflux was continued for 4 hours. Next, p-toluenesulfonic acid monohydrate (2.82 g, 14.8 mmol) was added and reflux was continued for 1 hour. Upon completion of the reaction, toluene was replaced with isopropanol (i-PrOH) and the volume of the solution was concentrated to approximately 30 mL. The solution was stirred overnight at room temperature to crystallize the product. The crystallized product was collected by filtration and washed with a small amount of isopropanol to give 2.01 g of 1-(2-fluoro-6-(trifluoromethyl)benzyl)-6-methylpyrimidine-2,4(1H,3H)-dione in 63% yield. The product was analyzed by LCMS (ESI) at m/z 303.0 (MH+).

References

[1] Patent: WO2009/62087, 2009, A1. Location in patent: Page/Page column 8

1-(2-Fluoro-6-(trifluoromethyl)benzyl)-6-methylpyrimidine-2,4(1H,3H)-dione(830346-47-9)Related Product Information

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