5-Hydroxypyrimidine

Tan Solid

A mixture of 77 (2.99 g, 27.2 mmol) and powdered potassium hydroxide (8.96 g of 85percent, 136 mmol) in methanol (50 mL) was heated in a sealed tube at 150° C. overnight. The mixture was cooled to room temperature, neutralized by the addition of acetic acid and concentrated under reduced pressure. The residue obtained was triturated with hot acetonitrile (2.x.100 mL) and the acetonitrile extracts concentrated under reduced pressure to afford 7.51 g of an off-white solid. This solid was triturated with hot ethyl acetate (100 mL) and the ethyl acetate extract concentrated under reduced pressure to afford 1.81 g of an off-white solid. Further purification by flash chromatography (silica, 9:1 methylene chloride/methanol) afforded 78 (1.11 g, 43percent) as an off-white solid: A mixture of 77 (2.99 g, 27.2 mmol) and powdered potassium hydroxide (8.96 g of 85%, 136 mmol) in methanol (50 mL) was heated in a sealed tube at 150 C. overnight. The mixture was cooled to room temperature, neutralized by the addition of acetic acid and concentrated under reduced pressure. The residue obtained was triturated with hot acetonitrile (2×100 mL) and the acetonitrile extracts concentrated under reduced pressure to afford 7.51 g of an off-white solid. This solid was triturated with hot ethyl acetate (100 mL) and the ethyl acetate extract concentrated under reduced pressure to afford 1.81 g of an off-white solid. Further purification by flash chromatography (silica, 9:1 methylene chloride/methanol) afforded 78 (1.11 g, 43%) as an off-white solid: 1H NMR (300 MHz, DMSO-d6) delta 10.45 (br s, 1H), 8.67 (s, 1H), 8.34 (s, 2H).Prepared as in Chem. Eur. J. 2003, 9, 4997-5010 on a 15 mmol scale with a yield of 27% after purification.1H NMR (DMSO^): delta 8.33 (s, 2H), 8.66 (s, IH), 10.45 (s, IH) ppmPreparation of The NaH (0.91 g, 22.8 mmol) was dissolved in DMF (15 ml), ethanethiol (0.84 ml, 11.4 mmol) was added to the solution, and the mixture was stirred at room temperature for 30 min. 5-methoxy pyrimidine (628 mg, 5.65 mmol) was added to the mixture and stirred at 100 C. for 4 hours. Subsequently, the product was filtered, washed, and dried to prepare NaH (0.91 g, 22.8 mmol) was dissolved in DMF (15 m), ethanethiol (0.84 m, 11.4 mmol) was added to the solution, and the mixture was stirred at room temperature for 30 min. 5-methoxy pyrimidine (628 mg, 5.65 mmol) was added to the mixture and stirred at 100 Cfor 4 hours. Subsequently, the product was filtered, washed, and dried to prepare b An autoclave is charged with 13.1 g (119 mmol) 5-methoxy-pyrimidine and 250 ml Methanol. 66.8 g (1.19 mol) KOH are added and the mixture is stirred at 125 C. over night. After this the mixture is neutralized with AcOH to pH 6-7 and then concentrated under vacuo. The residue is triturated four times with hot MeCN and the combined extracts are concentrated under vacuum. The resulting crude product is purified by flash chromatography (EtOAc 100%). C4H4N2O (M=96.09 g/mol) ESI-MS: 95 [M-H]-NaH (0.91 g, 22.8 mmol) was dissolved in DMF (15 ), ethanethiol (0.84 , 11.4 mmol) was added to the solution, and the mixture was stirred at room temperature for 30 min. 5-methoxy pyrimidine (628 , 5.65 mmol) was added to the mixture and stirred at 100 for 4 hours. Subsequently, the product was filtered, washed, and dried to prepare General procedure: Compound 6 (1.16g, 5.35mmol), 3-fluoro-5-hydroxypyridine (712mg, 6.30mmol), potassium carbonate (1.45g, 10.5mmol) and DMF (13mL) were added to a round-bottom flask and stirred at rt for 4h. The reaction was filtered and washed with ethyl acetate. The filtrate was washed with water (2×), and the aqueous layer was extracted with ethyl acetate. The combined organics were dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel afforded 1.50g (91%) of the title compound as a light brown solid

Molecular Weight:96.09
XLogP3:-0.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:96.032362755
Monoisotopic Mass:96.032362755
Topological Polar Surface Area:46
Heavy Atom Count:7
Complexity:51.7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes