4-Chloro-2-cyano-6-methylpyrimidine

To a solution of intermediate 1A (128.0 g, 889 mmol) and triethylamine (260 ml) in propionitrile (1.5 1) was added trimethylsilyl cyanide (334 ml, 2.67 mol). The mixture was stirred at reflux for26 h then left to stand at room temperature for 18 h. The reaction was quenched by the addition of30percent aqueous potassium carbonate solution and the layers were separated. The organic layer was washed with 10percent aqueous potassium carbonate solution, brine, dried over magnesium sulfate, filtered and concentrated. The resulting dark solid was recrystallized from hot isopropanol (150 ml) and water (300 ml) to give intermediate 2A (114.3 g, 84percent).c. PREPARATION OF 4-CHLORO-6-METHYLPICOLINONITRILE.[00398] 4-chloro-2-methylpyridine-N-oxide (8.97g, 62.5 mmol, 1 .00 eq) was dissolved in CHb. SYNTHESIS OF 4-CHLORO-6-METHYLPICOLINONITRILE (COMPOUND 2)To a solution of 4-chloro-2-methylpyridine-N-oxide(7, 4.3 kg, 29.94 mol) in dichloromethane (64.5 L, 15 V) was added trimethylsilyl cyanide (9.76 L, 77.83 mol) at 25–30 C over a period of 30 min and furtherstirred for 15 min. Reaction mass was cooled to 0–5 C. N, NDimethylcarbamoylchloride (7.17 L, 77.83 mol) was added drop wise over aperiod of 1 h. The reaction mass was slowly warmed to 25–30 C and stirred for36 h. Reaction was monitored by HPLC [7 NMT 1.0percent]. The reaction mass wascooled to 0-5 C. The reaction was quenched with 10percent aqueous potassiumcarbonate solution until the pH of aqueous layer was about 9–10. Thetemperature of reaction mass was allowed to attain 25–30 C and the layerswere separated. The aqueous layer was extracted with dichloromethane (8.6 L, 2 V). The combined organic layer was washed with 0.5 N HCl solution (21.5 L, 5 V) followed by brine solution (21.5 L, 5 V), dried over anhydrous sodiumsulfate and concentrated under vacuum. The residue was chased twice with nheptane(2 17.2 L). The crude product was diluted with 2percent ethyl acetate[Ashok alco-chem limited, Purity (areapercent) by GC – 100percent] in hexanes (43 L, 10 V)and filtered through silica plug (21.5 kg, 5percent w/w on SM, 230-400 mesh) andsilica plug was washed with 10percent ethyl acetate in hexanes till the product was completely eluted (300 L, 69 V). Combined fractions were concentrated andresidue was chased twice with n-heptane (2 17.2 L). Resulting mass wasstirred in n-heptane (21.5 L, 5 V) at 0–5 C for 1 h and filtered. Solid waswashed with cold n-heptane (4.3 L, 1 V) and dried to get 8 as off white solid(2.32 kg, 51percent).. 1H NMR (400 MHz, DMSO-d6) d 8.13 (d, J = 1.6 Hz, 1H), 7.82 (d, J = 1.7 Hz, 1H), 2.52 (s, 3H); 13C NMR (100 MHz, DMSO-d6) d = 161.99, 144.13, 133.01, 127.65, 126.40, 116.60, 23.57 ppm; LCMS (Method 1): RT = 0.715 min, m/z = 153.2 [M + H]+; HRMS, calc’d for C7H5ClN2 [M], 152.0141; found152.0139.

Molecular Weight:152.58
XLogP3:1.9
Hydrogen Bond Acceptor Count:2
Exact Mass:152.0141259
Monoisotopic Mass:152.0141259
Topological Polar Surface Area:36.7
Heavy Atom Count:10
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes