Pyrimidine, 4-chloro-5-fluoro- (9CI)

«tpr» 125.0 g 5-Fluoropyrimidin-4-ol was suspended in300 ml dichloromethane.33.7 ml Triethylamine was added, resulting in an almost clear solution. The reaction mixture was cooled with an ice-water bath.22.5 ml Phosphorus oxychloride was added dropwise over 15 minutes. The reaction mixture was allowed to warm to ambient temperature and the resulting purple suspension was stirred for 18 hours. Reaction progress was monitored with HPLC.300 ml Ice-water was carefully added to the reaction mixture and the two-phase system was stirred vigorously for 20 minutes. The organic layer was isolated and dried (Na2S04). The solvent was removed carefully on rota evaporator at 800-900 mbar, Twater bath- 50C. The last grams of solvent were removed by taking the flask out of the water bath and lowering the pressure to -250 mbar. To prevent loss of product, concentration was stopped when the total weight of the product was still a few gram above the theoretical 100% yield (= 29.05 g) and the product still contained some dichloromethane. 5-fluoro-4-chloropyrimidine was isolated as a dark orange oily liquid (99.3% purity acc. HPLC, NMR confirms expected structure). The product was used without further purification in the next step .Pd(Ph3P)4 (43.6 mg, 0.038 mmol) and 1, 1, 1, 2, 2, 2-hexamethyldistannane (124 mg, 0.377 mmol) were successively added to a mixture of 2, 4-Dichloro-5-fluoropyrimidine (7, 0.37 g, 2.2 mmol), sodium carbonate (0.42 g, 4 mmol) dissolved in 1, 4-dioxane/water (10 mL / 2 mL) Add bistriphenylphosphine palladium dichloride (Pd(PPh3)2Cl2, 0.033g, 0.048 mmol) under nitrogen, heat to 80 C, add 1-isopropyl-4-fluoro-6-borate A solution of the alcohol ester-1H-carbazole (6a, 0.5 g, 1.6 mmol) in 1, 4-dioxane (10 mL). The reaction 80 4 hours, the reaction was cooled to room temperature, poured into ice water (50 mL), the precipitated white solid was filtered to give the residue, recrystallized from isopropanol, to give a white solid 8a (0.4 g, 81%).1) Pyridinium chlorochromate, Sodium ferrate, Phosphoric acid and tetrabutylammonium chloride are added to the water, Pass argon as a protective gas, Then heated to 120 C as reactant A;Dissolving Prepare a dry, clean 1000mL glass four-necked flask with a suitable mechanical stirrer, condenser and thermometer, Pay attention to check the gas tightness before feeding, under N2 protection to the reaction flask was added 26.5g Step 1 To a solution of F7 (25 mg, 0.053 mmol) and Step 1 To a solution of A16 (25 mg, 0.056 mmol) and The compound 5 (1 mmol), The compound

Molecular Weight:132.52
XLogP3:1.3
Hydrogen Bond Acceptor Count:3
Exact Mass:131.9890539
Monoisotopic Mass:131.9890539
Topological Polar Surface Area:25.8
Heavy Atom Count:8
Complexity:80.4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes