3-Methyl-2-pyrazinamine

A mixture of 2-chloro-3-methylpyrazine (7 g, 54.69 mmol) and 25percent NHIn an autoclave, 2-chloro-3-methyl-pyrazine (1) (10.0 g, 77.8 mmol) was dissolved in dry methanol (30 mL). Ammonia gas (60 g) was added. The mixture was heated to 150°C for 8 hours. (start pressure: 10 bar, end pressure: 90 bar). After cooling to rt, the mixture was evaporated to a brown solid, which was dissolved in IN hydrochloric acid (100 mL) and washed with dichloromethane. The aqueous layer was slowly poured on cold saturated aqueous ammonia (150 mL), then extracted with dichloromethane (3 x 100 mL). The combined organic layers were dried (Na2SO4) and evaporated. The product was extracted from the residual solid with hot acetone (200 mL). Evaporation yielded 36 percent of 3-methyl-pyrazin-2- ylamine (2) as a yellow solidIn an autoclave, 2-chloro-3-methyl-pyrazine (1) (10.0 g, 77.8 mmol) was dissolved in dry methanol (30 mL) . Ammonia gas (60 g) was added. The mixture was heated to 15OA mixture of 2-chloro-3-methylpyrazine (7 g, 54.69 mmol) and 25percent NHIn an autoclave, 2-chloro-3-methyl-pyrazine (1) (10.0 g, 77.8 mmol) was dissolved in dry methanol (30 mL). Ammonia gas (60 g) was added. The mixture was heated to 150°C for 8 hours. (start pressure: 10 bar, end pressure: 90 bar). After cooling to rt, the mixture was evaporated to a brown solid, which was dissolved in IN hydrochloric acid (100 mL) and washed with dichloromethane. The aqueous layer was slowly poured on cold saturated aqueous ammonia (150 mL), then extracted with dichloromethane (3 x 100 mL). The combined organic layers were dried (Na2SO4) and evaporated. The product was extracted from the residual solid with hot acetone (200 mL). Evaporation yielded 36 percent of 3-methyl-pyrazin-2- ylamine (2) as a yellow solidIn an autoclave, 2-chloro-3-methyl-pyrazine (1) (10.0 g, 77.8 mmol) was dissolved in dry methanol (30 mL) . Ammonia gas (60 g) was added. The mixture was heated to 15OA suspension of 2-chloropyrazine (1) (250mg, 2.3mmol), 2-amino-3- methylpyrazine (2) (0.23mL, 2.5mmol), Cs2C03 (1.5g, 4.6mmol), Pd2(dba)3 (105mg, 0.12mmol) and Xantphos (148mg, 0.26mmol) in dioxane (15ml_) was degassed with Ar(g) for 20min. The reaction mixture was then heated up to 90C overnight. Once cooled down to rt, it was partitioned between EtOAc (35mL), H20 (10mL) and brine (5ml_). The organic phase was separated and the aqueous phase extracted with EtOAc (2 x 10ml_). The combined organics extracts were dried (MgS04) and concentrated in vacuo. Purification by SCX-2 with CH2CI2/MeOH (1 :0-1 :4) then 0.3M NH3 gave a residue. Pre-washed MP- TMT (ca. 400mg, 1.3mmol/g) was added to the residue dissolved in CH2CI2/MeOH (1 : 1 , 30ml_), which was then agitated overnight. The resin was removed by filtration and the solution concentrated in vacuo. Purification by silica gel column chromatography with hexane/EtOAc (1 :0-3:7) yielded (3) as a light yellow solid (310mg, 72%). (0401) LCMS (ES): Found 188.1 [M+Hf. (0402) 1H NMR (300 MHz, DMSO-cfe), d: 9.24 (s, 1 H), 9.10 (d, J=1.3 Hz, 1 H), 8.30 (dd, (0403) J= 2.6, 1.5 Hz, 1 H), 8.18 (d, J= 2.6 Hz, 1 H), 8.08-8.16 (m, 2H), 2.55 (s, 3H). (6 g, 55.0 mmol), 1-bromo-2-nitrobenzene (12.77 g, 63.2 mmol), cesium carbonate (35.7 g, 110 mmol), tris(dibenzylideneacetone)palladium(0) (1.509 g, 1.649 mmol) and BiNAP (4.10 g, 6.60 mmol) were charged into the reaction flask with 350 mL of toluene. This mixture was degassed with nitrogen then was heated at reflux for 16 h. GC/MS analysis showed this reaction to be complete. Heating was discontinued. The reaction mixture was filtered and concentrated under vacuum. The crude residue was subjected to column chromatography on silica gel, eluted with a gradient mixture of 2-5% ethyl acetate/toluene, yielding 3-methyl-N-(2-nitrophenyflpyrazin-2-amine (10 g, 43.4 mmol, 79% yield) as a yellow solid.

Molecular Weight:109.13
XLogP3:-0.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:109.063997236
Monoisotopic Mass:109.063997236
Topological Polar Surface Area:51.8
Heavy Atom Count:8
Complexity:74.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes