5-Pyrimidinecarboxylic acid, 2,4-dichloro-, ethyl ester

4-(3-fluorophenethylamino)-2-(1H-pyrazol-4-yl)-N-(pyridin-2-ylmethyl)pyrimidine-5-carboxamide Step i. Ethyl 2, 4-dichloropyrimidine-5-carboxylate To a 100 ml three-necked flask was added ethyl uracil-5-carboxylate (2.2 g, 11.95 mmol)N, N-dimethylaniline (2 g, 16.50 mmol).Under ice bath, phosphorus oxychloride (9.2 g, 60 mmol) was gradually added and stirred continuously.After the addition of 10 minutes, gradually heating 110 ° C, and insulation 3h reaction.The reaction solution was slowly poured into an ice-water mixture (100 ml) and quenched and kept at a temperature below 5 ° C. And extracted twice with ethyl acetate (200 ml).The organic phases were combined, washed with saturated brine, dried and concentrated to give the crude product.The crude product was purified by column chromatography to give 1.8 g of solid in 68percent yield.Step 2. A mixture of ethyl 2, 4-dioxo-l, 2, 3, 4-tetrahydropyrimidine-5-carboxylate obtained in step 1 (8.5 g, 46.2 mmol, 1.0 eq), N, N-dimethylbenzenamine (1.12 g, 9.24 mmol, 0.2 eq), POCl11.2: 2, 4-Dichloropyrimidine-5-carboxylic acid ethyl ester 9.2: 2, 4-Dichloropyrimidine-5-carboxylic Acid Ethyl Ester; In a 250 ml round-bottomed flask, under a nitrogen atmosphere, 13.5 g (64.0 mmol) of above compound are dissolved in 100 ml of anhydrous THF. 15 ml of absolute ethanol are added and the mixture is stirred for 10 min at ambient temperature. The mixture is diluted with a saturated aqueous solution of KEster 1.3 (22g, 120 mmol) was dissolved in phosphorous oxychloride(60 mL, 600 mmol) and the mixture treated with N, N-diethylaniline (27 mL, 167 mmol) and the mixture heated to 105Ester 1.3 (22g, 120 mmol) was dissolved in phosphorous oxychloride (60 niL, 600 mmol) and the mixture treated with N, N-diethylaniline (27 mL, 167 mmol) and the mixture heated to 105N, N-Diethylaniline (1.5 mL, 9.45 mmol) was added to a suspension of 5-carbethoxyuracil, i (1.00 g, 5.43 mmol), in phosphorus (V) oxychloride (10 mL). The mixture was heated under reflux for 2 h, cooled to room temperature and reduced in vacuo. The resulting syrupy residue was transferred carefully onto stirred ice / water (50 mL). After 1 h, the resulting beige solid was collected by filtration, washed with water (10 mL) and air-dried to give compound ii (0.97 g, 4.41 mmol, 81 percent) as a light beige powder. *Η NMR (300MHz, CDCL): δ 9.04 (1H, s), 4.46 (2H, q, / 7.2), 1.43 (3H, t, J 7.2); [M+H]To a mixture of ethyl 2, 4-dioxohexahydropyrimidine-5-carboxylate 2 (46.3 g, 0.251 mol) in 126 mL of POC was added N, N-diethylaniline (52.4 g, 0.351 mol). The mixture was stirred at 105 °C overnight. This mixture was cooled to r.t. and poured into ice, filtered to afford pale yellow solid. The solid was dissolved in 100 mL of DCM and dried over Na

Molecular Weight:221.04
XLogP3:2.3
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:219.9806328
Monoisotopic Mass:219.9806328
Topological Polar Surface Area:52.1
Heavy Atom Count:13
Complexity:191
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes