METHYL 2-AMINOPYRIMIDINE-5-CARBOXYLATE

To a solution of 2-amino pyridine (30 g, 0.31 mol) in DME (120 mL) was added chloro acetone (40.5 mL, 0.47 mol) at room temperature. The reaction mixture was heated to reflux, and then stirred for 48 hours. The volatiles were concentrated under reduced pressure. Then the residue was purified by column chromatography eluting with 1percent MeOH/DCM to afford Int-2 (20 g, 48percent) as a liquid. Mass (m/z): 133 [MStep f: To a mixture of guanidine hydrochloride (42.2 g, 0.44 mol) in DMF (300 mL) was added compound 206 (80 g, 0.40 mol). The resulting mixture was heated at 100 °C for 1 h.The reaction mixture was filtered before cooled. The filter cake was washed with 50 mLof DMF and the combined filtrate was concentrated to leave a residue which wassuspended in cold EtOH and washed with cold EtOH (50 mL) to afford the compound 207(38 g, 61.5percent) as a yellow solid. LCMS (m/z): 154.2 [M+if, i95.i[M+42f. ‘HNMR(400 MHz, CD3OD): ö 3.88 (s, 3H), 8.77 (s, 2H).Sodium (1Z)-2-(dimethoxymethyl)-3-methoxy-3-oxoprop-1-en-1-olate (1.37 g, 7.8 mmol) was diluted in DMF (12 mL), and guanidine hydrochloride (640 mg, 6.7 mmol) was added. The mixture was stirred at 100 Sodium (1Z)-2-(dimethoxymethyl)-3-methoxy-3-oxoprop-1-en-1-olate (1.37 g, 7.8 mmol) was diluted in DM F (12 mL), and guanidine hydrochloride (640 mg, 6.7 mmol) was added. The mixture was stirred at 100 °C for 1 h, then was cooled to rt and diluted with water. Methyl 2-aminopyrimidine-5-carboxylate precipitated as a light yellow solid, which was isolated by vacuum filtration (510 mg, 50percent): Preparation of 2-aminopyrimidine-5-carboxylicSodium (1 Z)-2-(dimethoxymethyl)-3-methoxy-3-oxoprop-1 -en-1 -olate was prepared as described by Zhichkin (Zhichkin et a/., 2002).Sodium (1 Z)-2-(dimethoxymethyl)-3-methoxy-3-oxoprop-1 -en-1 -olate (1.37 g, 7.8 mmol) was diluted in DMF (12 mL), and guanidine hydrochloride (640 mg, 6.7 mmol) was added. The mixture was stirred at 100 °C for 1 h, then was cooled to rt and diluted with water. Methyl 2- aminopyrimidine-5-carboxylate precipitated as a light yellow solid, which was isolated by vacuum filtration (510 mg, 50percent): Intermediate APreparation of 2-aminopyrimidine-5-carboxylic acidSodium (1 Z)-2-(dimethoxymethyl)-3-methoxy-3-oxoprop-1 -en-1-olate was prepared as described by Zhichkin (Zhichkin et al., 2002).Sodium (1 Z)-2-(dimethoxymethyl)-3-methoxy-3-oxoprop-1 -en-1 -olate (1.37 g, 7.8 mmol) was diluted in DMF (12 mL), and guanidine hydrochloride (640 mg, 6.7 mmol) was added. The mixture was stirred at 100 °C for 1 h, then was cooled to rt and diluted with water. Methyl 2- aminopyrimidine-5-carboxylate precipitated as a light yellow solid, which was isolated by vacuum filtration (510 mg, 50percent): The crude enolate from step 1 was dissolved in DMF (200 mL), and guanidine hydrochloride (64 g, 670 mmol) was added. The mixture was heated at 1 00 °C under N2 for 3 h. After cooling to rt, water was added and the mixture was cooled with an ice-water bath. The resulting precipitate was collected by vacuum filtration and dried under vacuum to give the desired product (63 g, 61 percent yield for 2 steps).Methyl 3, 3-dimethoxypropanoate ( 1 00 g, 675 mmol) and methyl formate (8 1 g, 1 350 mmol) were dissolved in anhydrous THF (450 mL). Sodium hydride (60percent dispersion; 32.4 g, 8 1 0 mmol, 1 .2 eq.) was then added slowly in portions at 0 °C. The reaction mixture was stirred at rt for 1 h, then was heated at 50 °C for 3 h. During this period, H2 evolution was observed. After cooling to rt, the solvent was then removed under reduced pressure to give the crude product which was directly used in the next step without further purification. The crude enolate from step 1 was dissolved in DMF (200 mL), and guanidine hydrochloride (64 g, 670 mmol) was added. The mixture was heated at 1 00 °C under Ni for 3 h. After cooling to rt, water was added and the mixture was cooled with an ice-water bath. The resulting precipitate was collected by vacuum filtration and dried under vacuum to give the desired product (63 g, 61 percent yield for 2 steps).Methyl 3, 3-dimethoxypropanoate ( 1 00 g, 675 mmol) and methyl formate (8 1 g, 1 350 mmol) were dissolved in anhydrous THF (450 mL). Sodium hydride (60percent dispersion; 32.4 g, 8 1 0 mmol, 1 .2 eq.) was then added slowly in portions at 0 °C. The reaction mixture was stirred at rt for 1 h, then was heated at 50 °C for 3 h. During this period, H2 evolution was observed. After cooling to rt, the solvent was then removed under reduced pressure to give the crude product which was directly used in the next step without further purification. The crude enolate from step 1 was dissolved in DMF (200 mL), and guanidine hydrochloride (64 g, 670 mmol) was added. The mixture was heated at 1 00 °C under N2 for 3 h. After cooling to rt, water was added and the mixture was cooled with an ice-water bath. The resulting precipitate was collected by vacuum filtration and dried under vacuum to give the desired product (63 g, 61 percent yield for 2 steps).Synthesized by the method described in Synthesis, 2002, 6, 720; 3, 3-dimethoxy-2-methoxy-carbonyl-propen-1-ol sodium salt (3.0g) and guanidine hydrochloride was dissolved in DMF (24mL). The mixture was stirred for 1 hour at 100°C. After cooling to room temperature, Was filtered off and water was added to the precipitated solid, After drying under reduced pressure, To give the title compound 720mg (30percent).To a 500-ml four-necked flask equipped with a stirring, thermometer, reflux condenser, and a 20 wt% sodium hydroxide aqueous solution tail gas absorption device, add 200 g of carbon tetrachloride, 20.0 g (0.2 mole) of methyl 2-methacrylate, 0.5 g of benzoyl peroxide, with stirring, Chlorine was intermittently introduced at 65-70 C, and a total of 29 grams of chlorine was introduced for 2 hours.The reaction was stirred at 65-70 C for 3 hours, and then nitrogen gas was bubbled for 1 hour to replace the residual chlorine and hydrogen chloride. Cool to room temperature, add 0.15 g of N, N-dimethylformamide, To eliminate benzoyl peroxide; intermittently pass in chlorine gas, and control the temperature not to exceed 40 C.A total of 15 g of chlorine gas was introduced for 2 hours, and the reaction was stirred at 40-45 C for 5 hours.Carbon tetrachloride was recovered by distillation. 300 g of methanol and 45 g of sodium hydroxide were added.30 grams of guanidine nitrate, stirred at 60-65 C for 4 hours, and distilled off the methanol, Add 120 g of dichloromethane to the residue, heat, and stir at 40-45 C for 1 hour.Filtrate while hot and recover dichloromethane.26.8 g of white powder crystal methyl 2-aminopyrimidine-5-carboxylate was obtained in a yield of 87.5%, The liquid purity was 99.3%.Synthesized by the method described in Synthesis, 2002, 6, 720; 3, 3-dimethoxy-2-methoxy-carbonyl-propen-1-ol sodium salt (3.0g) and guanidine hydrochloride was dissolved in DMF (24mL). The mixture was stirred for 1 hour at 100C. After cooling to room temperature, Was filtered off and water was added to the precipitated solid, After drying under reduced pressure, To give the title compound 720mg (30%).

Molecular Weight:153.14
XLogP3:-0.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:2
Exact Mass:153.053826475
Monoisotopic Mass:153.053826475
Topological Polar Surface Area:78.1
Heavy Atom Count:11
Complexity:143
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes