5-chloro-2,3-diMethylpyrazine

Under Ar(g), to a mixture of pyrazin-2-amine (1) (183mg, 1.9mmol), 5- chloro-2, 3-dimethylpyrazine (2) (250mg, 1.8mmol), Cs2C03 (1.14g, 3.5mmol) was added degassed dry 1 , 4-dioxane (13mL). The reaction mixture was then flushed with Ar(g) for 1 min before Pd2(dba)3 (80mg, 0.09mmol) and Xantphos (1 11 mg, 0.19mmol) were added. The reaction mixture was heated up to 90C for 40h. It was then cooled down to rt and concentrated in vacuo, CH2CI2 (15mL) and H20 (15mL) were added. The organic phase was separated and the water layer was extracted with EtOAc (15ml_). The organic layers were combined and Pd-scavenger (MP-TMT, ~400mg, 1.3mmol/g) was added. This was shaken for several hours followed by filtration. The filtrate was concentrated in vacuo, dissolved in DMSO (4ml_) and purified by basic prep LCMS to yield (3) as a solid (56mg, 16%).To a degassed solution of 1, 1-dimethylethyl (lR, 4S, 6R)-4-[(E/Z)-2-(4, 4, 5, 5-tetramethyl- l, 3, 2-dioxaborolan-2-yl)ethenyl]-3-azabicyclo[4.1.0]heptane-3-carboxylate D6 (150 mg) and Description 86: 2, 3-dimethyl-5-[(phenylmethyl)oxy]pyrazine (D86); Potassium tert-butoxide (413 mg, 3.68 mmol) was added to a solution of 5-chloro-2, 3- dimethylpyrazine D85 (350 mg) and benzyl alcohol (0.638 ml, 6.14 mmol) in 1, 4-Dioxane (12 ml). The resulting yellow suspension was stirred at 98 0C for 20 minutes and then the temperature was allowed to reach 23 0C. Water (5 ml) and EtOAc (20 ml) were added, the aqueous phase was extracted with EtOAc (3 x 10 ml) and the collected organic layers washed with brine (2 x 5 ml), dried over Na2SO4, filtered and evaporated under reduced pressure to give a yellow oil.This was purified by column chromatography on silica gel (SNAP KP-SiI 5Og; eluted with Cy/EtOAc 90:10) and an orange solid was obtained. It resulted to be not pure and it was further purified by silica gel chromatography (SNAP KP-SiI; eluted with n- hexane/Et2O 90:10). Evaporated fractions gave the title compound D86 as yellow solid(175 mg).UPLC (IPQC): rt = 1.10 minutes, peak observed: 215 (M+l) C13Hi4N2O requires 214.Description 85: In a 250 ml round-bottomed flask 2, 3-dimethylpyrazine 1 -oxide D55 (4.13 g) and POCl3 (31.0 ml, 333 mmol) were added and stirred at reflux for 3 hours. After this time the reaction mixture was cooled to room temperature and added into a 11 flask containing ice. The pH value of the medium was adjusted to 8 by the addition of solid KOH and then the mixture was extracted with EtOAc (5x200 ml). The organic phase was dried (Na2S04) and evaporated under reduced pressure to give a dark brown oil. This material was purified by column chromatography on silica gel (SNAP 100 g, Cy/EtOAc = from 9: 1 to 7:3) to afford the title compound D56 (722 mg) as yellow oil.UPLC (IPQC): rt = 0.70 minutes peak observed: 143 (M+l) C6H7C1N2 requires 142.1H NMR (400 MHz, CHLOROFORM-^ delta ppm 2.54 (s, 6 H) 8.32 (s, 1 H).2, 3-Dimethyl-pyrazine 1 -oxide (L2) (25 g, 0.2 mol) was dissolved in POCl3 (200 mL) under cooling. The mixture was gradually heated to reflux and stirred for 2 hrs. After cooling, the reaction mixture was poured onto ice, basified to pH 8 with a saturated KOH solution under cooling and extracted with EtOAc. The combined organics were dried over Na2SO4 and concentrated. The residue was purified by column (P.E./EtOAc 100:1-60: 1) to obtain 5-chloro-

Molecular Weight:142.58
XLogP3:1.5
Hydrogen Bond Acceptor Count:2
Exact Mass:142.0297759
Monoisotopic Mass:142.0297759
Topological Polar Surface Area:25.8
Heavy Atom Count:9
Complexity:97.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes