2-Chloropyrimidine-4-carbonitrile

Light yellow solid

Step 7) A mixture of 2-oxo-l, 2-dihydro-pyrimidi7ne-4-carbaldehyde oxime 10 (72.6 g) in cold (0 °C) phosphorus oxychloride (280 ml) was warmed slowly with vigorous stirring until a vigorous reaction commenced, at which time warming was discontinued. Once complete dissolution had taken place, N, N-diethylaniline (36.3 mL) was added and the reaction mixture was refluxed for another 30 minutes. After cooling to room temperature, the POClStep 2) Preparation of 2-chloro pyrimidine-4-carbonitrile; The compound obtained in Step 1 (4 g, 28.7 mmol) was added to 10 mi of trichlorophosphrous, and the mixture was stirred for 4 hours. The resulting mixture was concentrated under a reduced pressure to remove the solvent, and sequentially washed with sodium bicarbonate solution (200 ml*2) and salt solution. The resulting residue was subjected to silica gel column Prepared largely according to the method described in WO2005/075468. A solution of 4-methyl-lH-pyrimidin-2-one hydrochloride (14.7g, lOOmmol) in 50percent aqueous acetic acid (100ml) at 15°C was treated with sodium nitrite in one portion (10.4g, 150mmol) with vigorous stirring causing an exothermic reaction (40°C). A yellow precipitate was filtered off, washed with cold water and dried in a vacuum dessicator to afford the 2- hydroxy-pyrimidine-4-carbaldehyde oxime intermediate as a pale yellow solid (13. lg, 94percent) [0110] A solution of 4-methyl-1H-pyrimidin-2-one hydrochloride (14.7g, 100mmol) in 50percent aqueous acetic acid (100ml)at 15°C was treated with sodium nitrite in one portion (10.4g, 150mmol) with vigorous stirring causing an exothermicreaction (40°C). A yellow precipitate was filtered off, washed with cold water and dried in a vacuum dessicator to afford the 2-hydroxy-pyrimidine-4-carbaldehyde oxime intermediate as a pale yellow solid (13.1g, 94percent) 1H NMR (400 MHz, DMSO-d6) δ 12.44 (s, 1H), 11.87 (br s, 1H), 7.92 (d, J = 6.3 Hz, 1H), 7.77 (d, J = 0.4 Hz, 1H), 6.66 (dd, J = 6.4, 0.9 Hz, 1H). The oxime was treated with phosphorus oxychloride (20ml) and warmed slowly to 45°C. Warming was stopped asthe temperature rose suddenly to 70°C and the mixture stirred for 3h. Diisopropylethylamine (2ml) was added and themixture refluxed for 30mins before pouring into ice and extraction with DCM. The organics were washed with water thenNaHCO3 (sat aqu) then again with water, dried (MgSO4), filtered and evaporated to afford Intermediate IVd as a yellowoil which crystallized on standing (1.51g, 30percent). 1H NMR (400 MHz, DMSO-d6) δ 9.15 (d, J = 4.9 Hz, 1H), 8.25 (d, J =4.9 Hz, 1H).

Molecular Weight:139.54
XLogP3:1.2
Hydrogen Bond Acceptor Count:3
Exact Mass:138.9937248
Monoisotopic Mass:138.9937248
Topological Polar Surface Area:49.6
Heavy Atom Count:9
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes