4,6-dichloropyrimidine-5-carbonitrile

The starting material, 4, 6-DICHLORO-PYRIMIDINE-5-CARBONITRILE, used in the preparation of Compound A91 was prepared in the following manner: To a solution of 5-fomyl-4, 6- dichloropyrimidine (3.6 g, 20.3 mmol) in EtOAc (50 ML), was added a solution OF NH20H-HC1 (1.41 g, 20.3 mmol) in H2O (30 ML) followed by AcONa (1.67 g, 20.3 mmol) at rt. After stirring for 2h, the reaction was washed with H20 (50 ML, two times) and dried over MgS04. The EtOAc was concentrated under vacuum to afford the crude IMINOHYDROXY compound (3.51 g, 90.2percent). The crude compound was used for next step without further purification. The IMINOHYDROXY compound (3.51 g, 18.3 mmol) was dissolved in SOC12 (20 ML) at 0 °C and stirred for 30 min. The reaction was warmed to rt and maintained for 3h. The reaction was poured into H20 (100 g) portionwise and stirred for 30 min. The precipitate was filtered, washed with H2O (100 mL) and dried under vacuum to afford 4, 6-DICHLORO-PYRIRNIDINE-5-CARBONITRILE (2.99g, 91percent).APOS;H-NMR (DMSO-d6) : 8.53 ppm; LCMS: not detectable.4, 6-DICHLORO-PYRIMIDINE-5-CARBALDEHYDE (15.0 g, 84, 75 mmol, 1.0 equivalent) was dissolved in ethyl acetate (150 mL), mixed with hydroxylamine hydrochloride in water (30ML) and added sodium acetate. Reaction was at left room temperature for 1.5 hours. Worked up with ethyl acetate, sodium bicarbonate, dried with magnesium sulfate, rotovaped and dried and high vacuum to afford a white solid (14.593 g). The white solid (iminohydroxy intermediate) was added to thionyl chloride (100 mL) at 0° C with stirring and allowed to warm to room temperature for 3 hours. The reaction was quenched in ice (500G), and the precipitated was filtered off, washed with cold water, and dried under high vacuum to afford a white solid as product (10. 739g, 72. 8percent). 1H NMR 400MHZ CDC13 B (ppm): 8. 95 (s, LH, pyrimidine).

Molecular Weight:173.98
XLogP3:1.8
Hydrogen Bond Acceptor Count:3
Exact Mass:172.9547524
Monoisotopic Mass:172.9547524
Topological Polar Surface Area:49.6
Heavy Atom Count:10
Complexity:154
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes