4(1H)-PyriMidinone, 5-(4-broMophenyl)-6-hydroxy- Chemical Properties

Density 

1.74±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

pka

4.69±0.10(Predicted)

Appearance

White to yellow Solid

InChI

InChI=1S/C10H7BrN2O2/c11-7-3-1-6(2-4-7)8-9(14)12-5-13-10(8)15/h1-5H,(H2,12,13,14,15)

InChIKey

PIUMVXYVNAISNG-UHFFFAOYSA-N

SMILES

C1NC(O)=C(C2=CC=C(Br)C=C2)C(=O)N=1

Safety Information

HS Code 

2933599590

4(1H)-PyriMidinone, 5-(4-broMophenyl)-6-hydroxy- Usage And Synthesis

Uses

5-(4-Bromophenyl)pyrimidine-4,6-diol is used in preparation of pharmaceutical intermediate of Macitentan.

Synthesis

To a stirred solution of 100 g of dimethyl 2-(4-bromophenyl)malonate (0.348 mol) dissolved in 400 cm3 methanol at 20-25 °C, 30 g of formamide (0.66 mol) and 30 g of sodium methanolate (0.555 mol) were added sequentially. The reaction mixture was heated to 70 °C and maintained at this temperature until the reaction was complete (monitored by HPLC). After completion of the reaction, methanol was removed by distillation under reduced pressure at 70°C to give a syrupy substance. The syrup was cooled to 25-30 °C and diluted with 2 dm3 water. The pH of the solution was adjusted to 2-2.5 with concentrated hydrochloric acid and this pH was maintained for 45 min. The precipitated solid was collected by filtration and washed with water until the filtrate reached pH 7-7.5. The product was blotted dry and dried under reduced pressure at 100°C to give the crude product 5-(4-bromophenyl)-6-hydroxypyrimidin-4(1H)-one. The crude product was dissolved in 500 cm3 methanol and heated to 60-65°C and kept for 1 hour. The reaction mixture was then cooled to 25-30°C and left to stand for 30 minutes. The resulting solid was filtered, washed with methanol and dried under reduced pressure at 50-55°C to give the pure product 5-(4-bromophenyl)-6-hydroxypyrimidin-4(1H)-one. Yield: 70 g (75.25%); HPLC purity: 99.5%; melting point: 176-180 °C. The spectral data of the obtained compounds were in agreement with literature reports [8].

References

[1] Monatshefte fur Chemie, 2018, vol. 149, # 3, p. 653 - 661

4(1H)-PyriMidinone, 5-(4-broMophenyl)-6-hydroxy-(706811-25-8)Related Product Information

• Macitidine related impurities
• PropylsulfaMide
• CarbaMic acid, N-[(propylaMino)sulfonyl]-, phenylMethyl ester
• N-Propylsulfuric diamide-sodium
• SulfaMide, N-propyl-,(potassiuM salt)(1:1)
• Macitentan impurity A
• 5-Bromo-2-chloropyrimidine
• 5-(4-Bromophenyl)-4,6-dichloropyrimidine
• 2-(4-BROMOPHENYL)-PROPANEDIOIC ACID, 1,3-MDIETHYL ESTER
• Macitentan impurity B
• macitentan
• ACT 080803
• Macitentan IMpurity
• Masitatin impurity 1
• NA
• Macitidine impurity 2
• Masitatin impurity 3
• Macitidine impurity 5