5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine

To a solution of 3, 5-dibromopyrazin-2-amine (2.00 g, 7.91 mmol) in THF (24 mL)were added triethylamine (3.3 mL, 24 mmol), cuprous iodide (151 mg, 0.79 mmol) andPd(PPh3hCh (561 mg, 0.79 mmol). The mixture was cooled to -5 oc under nitrogen protection, then trimethylsilylacetylene (1.07 mL, 7.50 mmol) was dropwised slowly into the mixture. Afterthe addition, the mixture was warmed to 0 oc and stirred for 1.5 h. The mixture was concentratedin vacuo to remove the solvent and the residue was purified by silica gel column chromatography(PE/EtOAc (v/v) = 511) to give the title compound as black oil (42 mg, 94 percent).MS (ESI, pos. ion) m/z: 272.00 [M+Ht;1H NMR (400 MHz, CDCh) 8 (ppm): 8.04 (s, lH), 5.14 (s, 2H), 0.30 (s, 9H).Ice bath, 3, 5-dibromopyrazine-2-amine (16.30 g, 64.50 mmol), cuprous iodide (2.45 g, 12.90 mmol)Tetraphenylphenylphosphine palladium (3.70 g, 3.20 mmol)And N, N-dimethylformamide (80 mL) was placed in a single-necked flask, Under N2, triethylamine (44.8 mL, 321 mmol) was added, Trimethylsilylacetylene (8.7 mL, 61.3 mmol) was slowly added dropwise over 10 min, After the dropwise addition, the mixture was stirred at room temperature for 1 h. Filtered, washed with dichloromethane (100 mL) and the filtrate was concentrated, The concentrate was subjected to column chromatography (eluent: PE / EtOAc (v / v) = 20/1) to give 14.70 g of a white solid, yield:84.4percent.Step 1 : 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine(Trimethylsilyl)acetylene (1.845 g, 2.655 niL, 18.78 mmol) was added dropwise to a solution of 3, 5-dibromopyrazin-2-amine (5 g, 19.77 mmol), triethylamine (10.00 g, 13.77 mL, 98.85 mmol), Copper(I) iodide (451.7 mg, 2.372 mmol) and Pd(PPh[00195] Step 1 : (Trimethylsilyl)acetylene (1.9 g, 2.7 niL, 18.8 mmol) was added dropwise to a solution of 3, 5-dibromopyrazin-2-amine (5.0 g, 19.8 mmol), triethylamine (10.0 g, 13.8 mL, 98.9 mmol), copper (I) iodide (452 mg, 2.37 mmol) and Pd(PPh(Trimethylsilyl)acetylene (1.845 g, 2.655 mL, 18.78 mmol) was added dropwise to a solution of 3, 5-dibromopyrazin-2-amine 1 (5 g, 19.77 mmol) in DMF (25 mL)Triethylamine (10.00 g, 13.77 mL, 98.85 mmol), copper(I) iodide (451.7 mg, 2.372 mmol) and Pd(PPh[00178] (Trimethylsilyl)acetylene (1.845 g, 2.655 mL, 18.78 mmol) was added dropwise to a solution of 3, 5-dibromopyrazin-2-amine 1 (5 g, 19.77 mmol) in DMF (25 mL)Triethylamine (10.00 g, 13.77 mL, 98.85 mmol), copper(I) iodide (451.7 mg, 2.372 mmol) and Pd(PPh(Trimethylsilyl)acetylene (1.845 g, 2.655 mL, 18.78 mmol) was added dropwise to a solution of 3, 5-dibromopyrazin-2-amine (compound i) (5 g, 19.77 mmol) in DMF (25 mL). Triethylamine (10.00 g, 13.77 mL, 98.85 mmol), copper(I) iodide (451.7 mg, 2.372 mmol) and Pd(PPh5-Bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine 2 [00178] (Trimethylsilyl)acetylene (1.845 g, 2.655 mL, 18.78 mmol) was added dropwise to a solution of 3, 5-dibromopyrazin-2-amine 1 (5 g, 19.77 mmol) in DMF (25 mL) Triethylamine (10.00 g, 13.77 mL, 98.85 mmol), copper(I) iodide (451.7 mg, 2.372 mmol) and Pd(PPhStep 1: Synthesis of 5-Bromo-3-trimethylsilanylethynyl-pyrazm-2-yIamine.[0282] To a solution of 3, 5-Dibromo-pyrazin-2-ylamine (3.00 g, 11.86 mmol) in DMF(35 ml) was added triethylamine (16 ml), then tetraldstriphenylphine palladium (0) (685 mg, 0.59 mmol) and copper(i) iodide (271 mg, 1.42 mmol) were added sequentially. Finallytrimethylsilylacetylene (2.0 ml, 14.3 mmol) was added dropwise. The reaction mixture wasstirred at 120 °C for 30 minutes and then directly adsorbed onto silica gel. Purification byflash chromatography on silica gel with a gradient of ethyl acetate/hexane afforded the titlecompound (2.30g, 71percent yield) as yellow oil. MS: m/z 270.0/272.0 [MH+].To a solution of 3, 5-dibromopyrazin-2-amine (40.0 g, 158 mmol), TEA (66.1 mL, 475 mmol), and copper(I) iodide (0.301 g, 1.58 mmol) in THF (1172 ml) was added PdClTo a solution of 3, 5-dibromopyrazin-2-amine (10 g, 40 mmol), copper(I) iodide (0.91 g, 4.7 mmol), diisopropylethylamine (53 mL, 0.55 mol), and tetrakis(triphenylphosphine)-palladium(0) (2.3 g, 1.9 mmol) in DMF (120 mL) that was de-gassed with Ar was added trimethylsilylacetylene (6.7 mL, 48 mmol). The resulting mixture was stirred under an Ar atmosphere for 1 h at 120Preparation of 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (Intermediate AQ) [0313] To a solution of 3, 5-dibromopyrazin-2-amine (10 g, 40 mmol), copper(I) iodide (0.91 g, 4.7 mmol), diisopropylethylamine (53 mL, 0.55 mol), and tetrakis(triphenylphosphine)- palladium(O) (2.3 g, 1.9 mmol) in DMF (120 mL) that was de-gassed with Ar was added trimethylsilylacetylene (6.7 mL, 48 mmol). The resulting mixture was stirred under an Ar atmosphere for 1 h at 120°C, after which it was evaporated to dryness in vacuo. The residue was subjected to silica gel chromatography eluting with 35percent EtOAc in hexanes to give a brown oil that was triturated with hexanes to give the title compound (5.0 g, 47percent). 1H NMR (CDC1Making reference to Scheme 5, to a solution of 3, 5-dibromopyrazin-2-amine (10 g, 40 mmol), copper(I) iodide (0.91 g, 4.7 mmol), diisopropylethylamine (53 mL, 0.55 mol), and tetrakis(triphenylphosphine)-palladium(0) (2.3 g, 1.9 mmol) in DMF (120 mL) that was de-gassed with Ar was added trimethylsilylacetylene (6.7 mL, 48 mmol). The resulting mixture was stirred under an Ar atmosphere for 1 h at 120°C, after which it was evaporated to dryness in vacuo. The residue was subjected to silica gel chromatography eluting with 35percent EtOAc in hexanes to give a brown oil that was triturated with hexanes to give the title compound (5.0 g, 47percent). To a solution of intermediate I-82 (10 g, 40 mmol, 1.0 eq) in DMF (115 mL) was added neat triethylamine (53 mL), Pd(PPhStep 1 A 500 ml three necked round bottom flask was charged with 3, 5-dibromopyrazine-2- amine (25.0 g, 0.0988 mole) which was dissolved in acetonitrile (250 ml). The reaction mixture was cooled to 0 ° C and triethylamine (50.0 g, 0.4941 mole), copper (1) iodide (2.26 g, 0.0119 mole), and Pd (PPh

Molecular Weight:270.20
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:268.99839
Monoisotopic Mass:268.99839
Topological Polar Surface Area:51.8
Heavy Atom Count:14
Complexity:262
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes