4(1H)-Pyrimidinone,5-fluoro-6-hydroxy-2-methyl-(9CI)

Part A: 5-Fluoro-4, 6-dihydroxy-2-methylpyrimidine. A solution of 200 ml. of 25percent wt sodium methoxide in methanol (0.84 mol) was diluted with an additional 200 ml. of methanol. Acetamidine-HCI (40 g , 0.42 mol) was added to the sodium methoxide solution (white precipitate formed), followed by addition of dimethyl fluoromalonate (70 g, 0.46 mol). The contents were stirred at room temperature overnight, then concentrated in vacuo to dryness. The resulting residue was redissolved in hot water (300 ml_). After cooling the aqueous solution to room temperature, concentrated HCI was added slowly until crystal formation (fine white prisms) took place at about pH 5. Concentrated HCI was added dropwise until pH 3, and then the contents were filtered. The isolated crystals were rinsed with 1 M HCI and dried under vacuum to provide 5-fluoro-4, 6-dihydroxy-2-methylpyrimidine (65.5 g, >100percent). LCMS: (M+H)Part A: 5-Fluoro-4, 6-dihydroxy-2-methylpyrimidine A solution of 200 ml. of 25percent wt sodium methoxide in methanol (0.84 mol) was diluted with an additional 200 ml. of methanol. Acetamidine-HCI (40 g , 0.42 mol) was added to the sodium methoxide solution (white precipitate formed), followed by addition of dimethyl fluoromalonate (70 g, 0.46 mol). The contents were stirred at room temperature overnight, then concentrated in vacuo to dryness. The resulting residue was redissolved in hot water (300 ml_). After cooling the aqueous solution to room temperature, concentrated HCI was added slowly until crystal formation (fine white prisms) took place at about pH 5. Concentrated HCI was added dropwise until pH 3, and then the contents were filtered. The isolated crystals were rinsed with 1 M HCI and dried under vacuum to provide 5-fluoro-4, 6-dihydroxy-2-methylpyrimidine (65.5 g, >100percent). LCMS: (M+H)Part A: Part A: 5-Fluoro-4, 6-dihydroxy-2-methylpyrimidine. A solution of 200 ml. of 25% wt sodium methoxide in methanol (0.84 mol) was diluted with an additional 200 ml. of methanol. Acetamidine-HCI (40 g , 0.42 mol) was added to the sodium methoxide solution (white precipitate formed), followed by addition of dimethyl fluoromalonate (70 g, 0.46 mol). The contents were stirred at room temperature overnight, then concentrated in vacuo to dryness. The resulting residue was redissolved in hot water (300 ml_). After cooling the aqueous solution to room temperature, concentrated HCI was added slowly until crystal formation (fine white prisms) took place at about pH 5. Concentrated HCI was added dropwise until pH 3, and then the contents were filtered. The isolated crystals were rinsed with 1 M HCI and dried under vacuum to provide Part A: 5-Fluoro-4, 6-dihydroxy-2-methylpyrimidine A solution of 200 ml. of 25% wt sodium methoxide in methanol (0.84 mol) was diluted with an additional 200 ml. of methanol. Acetamidine-HCI (40 g , 0.42 mol) was added to the sodium methoxide solution (white precipitate formed), followed by addition of dimethyl fluoromalonate (70 g, 0.46 mol). The contents were stirred at room temperature overnight, then concentrated in vacuo to dryness. The resulting residue was redissolved in hot water (300 ml_). After cooling the aqueous solution to room temperature, concentrated HCI was added slowly until crystal formation (fine white prisms) took place at about pH 5. Concentrated HCI was added dropwise until pH 3, and then the contents were filtered. The isolated crystals were rinsed with 1 M HCI and dried under vacuum to provide Part A: A mixture of sodium metal (1.55 g, 67.4 mmol) and EtOH (15.0 mL, 257 mmol) was stirred at RT until nearly all sodium had reacted. Diethyl fluoromalonate (3.54 mL, 22.4 mmol) was added followed by acetamidine hydrochloride (2.14 g, 22.7 mmol). The reaction mixture was heated at reflux for 3 h, cooled to RT and concentrated under reduced pressure. The residue was diluted with water (ca. 50 mL) and acidified (pH=2) with 6M aqueous HCl, and the mixture was stirred at RT for 1 h as a precipitate formed. The solids were collected by suction filtration and washed with water. Excess solvent was removed in vacuo to give Part A: A mixture of sodium metal (1.55 g, 67.4 mmol) and EtOH (15.0 mL, 257 mmol) was stirred at RT until nearly all sodium had reacted. Diethyl fluoromalonate (3.54 mL, 22.4 mmol) was added followed by acetamidine hydrochloride (2.14 g, 22.7 mmol). The reaction mixture was heated at reflux for 3 h, cooled to RT and concentrated under reduced pressure. The residue was diluted with water (ca. 50 mL) and acidified (pH = 2) with 6M aqueous HCl, and the mixture was stirred at RT for 1 h as a precipitate formed. The solids were collected by suction filtration and washed with water. Excess solvent was removed in vacuo to give

Molecular Weight:144.10
XLogP3:-0.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Exact Mass:144.03350557
Monoisotopic Mass:144.03350557
Topological Polar Surface Area:61.7
Heavy Atom Count:10
Complexity:244
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes