5-Pyrimidinamine

Pyrimidin-5-amine is an aminopyrimidine.

A solution of 5-amino-4, 6-DICHLOROPYRIMIDINE (5.0 g, 30.5 mmol) in 250 mL of diethyl ether was treated with sodium hydroxide solution (20.0 g, 0.50 mol, in 60 ML of water) and palladium (10percent on carbon, 400 mg). The mixture was shaken at room temperature on a Parr shaker under 50 psi of hydrogen gas for 20 hours. The mixture was filtered through CELTES filter aid. The phases were separated and the aqueous layer was extracted with three 100 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Crystallization of the crude from ethyl acetate gave pyrimidin-5-ylamine as white crystalline solid (2.8 g; 95percent yield). Bromination of pyrimidin-5-ylamine was performed in the same manner as for the preparation of 4-AMINO-3-BROMO-2, 6-dimethylpyridine. The resulting crude product (300 mg, 35percent yield) was deemed pure and used without further purification. Alternatively, 5-amino-4-bromopyrimidine can be synthesized according to the following procedure: A solution of 4, 6-dichloro-5-aminopyrimidine (21 g, 128 mmol) in 250 mL of MeOH was sequentially treated with ammonium formate (45 g, 714 mmol) and palladium (10percent on charcoal, 1 g, 0.943 mmol) at 0 C. The mixture was stirred overnight at room temperature and was filtered through CELITEO filter aid. The filtrate was concentrated to give a yellow solid. 100 mL of water and 250 mL of ethyl acetate were added. The organic phase was separated and the aqueous layer was extracted with eight 250 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo to yield off-white crystals (8. 1 g, 67percent). A stirred solution OF 5-AMINOPYRIMIDINE (3.0 g, 31.5 mmol) in 150 mL of dichlromethane and 30 mL of methanol was cooled to 0 C. Benzyltrimethylammonium tribromide (13.5 g, 34.7 mmol) was added in portions over a period of 10 minutes. Stirring was continued at 0 C for 15 minutes and at room temperature for 90 minutes. The reaction mixture was treated with aqueous sodium bicarbonate solution until the solution was pH 8. The organic layer was separated and aqueous layer was extracted with three 30 mL portions of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. An off-white solid (2. 8 g; 51percent) was obtained, which was used without further purification.A solution of 5-amino-4, 6-DICHLOROPYRIMIDINE (5.0 g, 30.5 mmol) in 250 mL of diethyl ether was treated with sodium hydroxide solution (20.0 g, 0.50 mol, in 60 ML of water) and palladium (10percent on carbon, 400 mg). The mixture was shaken at room temperature on a Parr shaker under 50 psi of hydrogen gas for 20 hours. The mixture was filtered through CELTES filter aid. The phases were separated and the aqueous layer was extracted with three 100 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Crystallization of the crude from ethyl acetate gave pyrimidin-5-ylamine as white crystalline solid (2.8 g; 95percent yield). Bromination of pyrimidin-5-ylamine was performed in the same manner as for the preparation of 4-AMINO-3-BROMO-2, 6-dimethylpyridine. The resulting crude product (300 mg, 35percent yield) was deemed pure and used without further purification. Alternatively, 5-amino-4-bromopyrimidine can be synthesized according to the following procedure: A solution of 4, 6-dichloro-5-aminopyrimidine (21 g, 128 mmol) in 250 mL of MeOH was sequentially treated with ammonium formate (45 g, 714 mmol) and palladium (10percent on charcoal, 1 g, 0.943 mmol) at 0 C. The mixture was stirred overnight at room temperature and was filtered through CELITEO filter aid. The filtrate was concentrated to give a yellow solid. 100 mL of water and 250 mL of ethyl acetate were added. The organic phase was separated and the aqueous layer was extracted with eight 250 mL portions of ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo to yield off-white crystals (8. 1 g, 67percent). A stirred solution OF 5-AMINOPYRIMIDINE (3.0 g, 31.5 mmol) in 150 mL of dichlromethane and 30 mL of methanol was cooled to 0 C. Benzyltrimethylammonium tribromide (13.5 g, 34.7 mmol) was added in portions over a period of 10 minutes. Stirring was continued at 0 C for 15 minutes and at room temperature for 90 minutes. The reaction mixture was treated with aqueous sodium bicarbonate solution until the solution was pH 8. The organic layer was separated and aqueous layer was extracted with three 30 mL portions of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. An off-white solid (2. 8 g; 51percent) was obtained, which was used without further purification.Example 142; 4-(3-Phenyl-1, 2, 4-thiadiazol-5-yl)-N-pyrimidin-5-ylpiperazine-1-carboxamide; (1) Pyrimidine-5-amine; A mixture of 5-amino-4, 6-dichloropyrimidine (2.00 g, 12.2 mmol), ether (240 ml), sodium hydroxide (8 g), water (32 ml) and 10percent palladium-carbon (160 mg) was stirred under a hydrogen atmosphere at room temperature for 3 days, insolubles were filtered off and an organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure to obtain the desired product (370 mg, 31.9percent) as a solid.

Molecular Weight:95.10
XLogP3:-0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:95.048347172
Monoisotopic Mass:95.048347172
Topological Polar Surface Area:51.8
Heavy Atom Count:7
Complexity:48.9
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes