2-Amino-5-bromopyrazine

Brown Needles

2-Amino-5-bromopyrazine (15).; To a cooled solution of 2-aminopyrazine 11 (2.00 g, 21.00 mmol) in dichloromethane (50 mL) N-bromosuccinimide (NBS) (3.73 g, 21.00 mmol) was added in portion. The mixture was stirred at 0 /-Bromosuccinimide (8.98 g, 50 mmol) was added portionwise over 15 minutes to a solution of 2-aminopyrazine (4.75 g, 50 mmol) in dichloromethane (300 mL) at OA light yellow solution of 19.0 g (0.20 mol) of 2-aminopyrazine in 40 ml of DMF and 120 ml of acetonitrile, and a light yellow solution of 30.0 g (0.10 mol) of 1 , 3-dibromo-5, 5- dimethylhydantoin (DBH) in 20 ml of DMF and 180 ml of acetonitrile are simultaneously added during 30 minutes under argon from two dropping funnels at -5°C to pre-cooled 20 ml of acetonitrile. After addition the resulting brown solution is treated with 40 ml of a 10percent-solution of sodium thiosulfate at -5°C providing a brown suspension and stirring continued until room temperature is reached. The reaction mixture is concentrated under vacuum and 180 ml of aqueous 2percent-solution of sodium carbonate added, followed by the addition of 10 g of HyfloPreparation c-119 To a solution of pyrazin-2-ylamine (2. 0 g, 21. 03 mmol) in dry DICHLOROMETHANE (120 mL) at 0 °C, was added N-BROMOSUCCINIMIDE (3. 74 g, 21. 03 mmol) slowly to maintain the internal temperature below 0 °C. The mixture was stirred at the same temperature for 24 hours, and then washed with saturated aqueous sodium bicarbonate (30 mL) and water (30 mL). The combined aqueous extracts were extracted with DICHLOROMETHANE (3 x 100 mL). The combined organic extracts were dried (anhydrous magnesium sulfate), filtered, and concentrated in vacuo to afford the crude product. The residue was purified by flash column chromatography (10percent to 50percent ethyl acetate/hexanes) to yield the title compound (2. 57 g, 70percent) as a yellow solid. LRMS (m/z) : 174 (M)-. 'H NMR (CDCI3, 300 MHz) : 8. 08 (1H, d, J= 1. 3 Hz), 7. 76 (1H, D, J= 1. 3 Hz).To a solution of pyrazin-2-amine (30 g, 0.32 mmol) in DCM (900 mL) at 0 °C was added NBS (56 g, 0.32 mmol). The reaction mixture was stirred at ambient temperature for 3 h and then washed with sat. NaHCO3 and brine. The organic layer was dried over anhydrous Na2504, filtered and concentrated to afford 5 -bromopyrazin-2-amine (38 g, 70 percent) as a white solid whichwas used directly in the next step.Under absence of light and at 0° C., N-bromosuccinimide (7.84 g, 44.05 mmol) was added to a solution of 2-aminopyrazine (4.19 g, 44.06 mmol) in dry dichloromethane (250 ml). Step 1: Step 1: To a [CH2C12] (150 mL) solution of aminopyrazine (1) (5.90 g, 62 mmol) in an ice bath was added N-bromosuccinimide (NBS, 11.1 g, 62 mmol) as a solid. The resulting mixture was stirred for 1 hr to form a brown slurry. The slurry was poured into 2 N [NA2C03] (150 mL), and extracted with [CH2C12] [(3X100] mL). The combined organic extracts were washed with brine, dried over [MGS04, ] and evaporated to afford a brown solid. The crude material was purified on silica gel (eluting with 20-40percent ethyl acetate in hexane) to afford 5.80 g (54percent yield) of the desired compound (2) as an off-white solid. LCMS: [M/Z =] 174.0, 176.0 [(M+H).]To a solution of 2-aminopyrazine (i) (2 g, 21.02 mmol) in dry DCM (10 ml) was added NBS (3.78 g, 21.23 mmol) portion-wise under cold condition and the resulting mixture was allowed to stir at RT for 6h. 5 ml of water was added and the layers were separated. Aqueous layer was extracted with DCM (10 ml X 2). Combined organic layers were washed with Brine solution (5 ml), dried over anhydrous Na2-Aminopyrazine (Aldrich, 20 g, 0.21 mol) was dissolved in 600 mL of CHTo a suspension of 2-aminopyrazine (1) (20.0 g, 210.28 mmol) in dry DCM (200 mL) was added N-bromosuccinimide (37.42 g, 210.28 mmol) in portion wise at cold condition under nitrogen atmosphere and stirred at RT for 1.5 h. Reaction mixture was concentrated under vacuum, added 30 mL of water and filtered the crude solid. Filtrate was extracted with DCM:MeOH (9: 1, 50 mL X 4). Combined organic layers was washed with brine solution (20 mL), dried over anhydrous NaExample 17-1 5-bromopvrazin-2-amine (M); To a solution of 2-aminopyrazine (1.00 g, 10.0 mmol) in chloroform (50 mL) and pyridine (0.8 mL, 10.0 mmol), solid pyridineNo.HBr3 (3.37 g, 10.0 mmol) was added in portions over 10 min. The reaction mixture was stirred at room temperature for 2 h. Saturated NaHCOs aqueous solution (25 mL) was added to this reaction mixture carefully (pH 7 to 8) and stirred for 10 min. Organic layer was separated, washed with water (15 mL x 3) (filtered if necessary), dried with Na2S04, filtered, and evaporated to dryness. The residue was purified using column chromatography (silica gel, 1:1:8 hexane/CH2CI2/EtOAc). The fractions containing product were evaporated to dryness under vacuum to yield compound M as a pale yellow solid (601 mg, 3.45 mmol, 35percent). NBS (45 g, 253 mmol) was added in portions to a suspention of 2- aminopyrazine (25 g, 263 mmol) in dichloromethane (500 ml) over a period of 2h. The mixture was filtered and evaporated. The residue was suspended in dichloromethane (60 ml) and stirred for 10 minutes before hexane (60 ml) was added. The mixture was stirred vigorously for 15 minutes and filtrated. The yellow powder was washed with CH2CI2/ hexane 1 : 1 (3x). The solid was dis- solved in diethylether and washed with water (3x), dried (mgso4) and evaporated, yield: 15.0 g (33percent). Light yellow solid. HPLC 95percent Rt=I .04 (system A. 10- 97percent MeCN over 3 minutes). HPLC 95percent Rt=O.78 (system B. 10-97percent MeCN over 3 minutes). MS (elecronspray; [M+H}+ 174.4. IH NMR (400 MHz, CHLORO- FORM-D) δ ppm 4.60 (s, 2 H) 7.76 (d, J= I .51 Hz, 1 H) 8.08 (d, J= I .51 Hz, 1 H).

Molecular Weight:174.00
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:172.95886
Monoisotopic Mass:172.95886
Topological Polar Surface Area:51.8
Heavy Atom Count:8
Complexity:77.7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes