2-BROMO-7-IODO-5H-PYRROLO[2,3-B]PYRAZINE

Step 1. 2-Bromo-7-iodo-5H-pyrrolo[2, 3-b]pyrazine. To a solution of 2-bromo-5H-pyrrolo[2, 3-b]pyrazine (8 g, 40.4 mmol) in DMF (160 mL) was added N-iodosuccinimide (11.8 g, 3.6 mmol) at room temperature, and stirred for 1 h. TLC (Petroleum ether: EtOAc, 2:1) indicated the reaction was completed. reaction mixture was diluted with water (500 mL), and extracted with EtOAc (300 mL×3). The combined organic layers were washed with brine, and dried over Na2-bromo-7-iodo-5H-pyrrolof3, 2-blpyrazine CIV-E-I); A mixture of III-E-1 (5.0 g, 25 mmol; commercially available from Ark pharma) and freshly ground KOH (5.10 g, 90.9 mmol) in DMF (100 mL) was stirred at RT under NTo a solution of 2-bromo-5H-pyrrolo[3, 2-Z?]pyrazine [Intermediate AS] (0.68 g, 3.4 mmol) in acetone (17 mL) was added N-iodosuccinimide (0.82 g, 3.6 mmol) and the resulting mixture was stirred for 4 h at rt. The mixture was evaporated in vacuo to yield a residue that was purified via silica gel chromatography eluting with 40percent TΗF in hexanes to give the title compound as a yellow solid (0.99 g, 89percent). Preparation of 2-bromo-7-iodo-5H-pyrr lo [3, 2-6] yrazine (Intermediate AT)[0316] To a solution of 2-bromo-5H-pyrrolo[3, 2-.pound.]pyrazine [Intermediate AS] (0.68 g, 3.4 mmol) in acetone (17 mL) was added N-iodosuccinimide (0.82 g, 3.6 mmol) and the resulting mixture was stirred for 4 h at rt. The mixture was evaporated in vacuo to yield a residue that was purified via silica gel chromatography eluting with 40percent THF in hexanes to give the title compound as a yellow solid (0.99 g, 89percent). 1H NMR (DMSO-dtf, 300 MHz): δ 12.82 (s, 1H), 8.42 (s, 1 H), 8.20 (s, 1 H). HPLC retention time: 2.23 minutes. MS ESI (m/z): 324.0, 326.0 (M+H)To a solution of 2-bromo-5H-pyrrolo[3, 2-Z?]pyrazine (0.68 g, 3.4 mmol) in acetone (17 mL) was added N-iodosuccinimide (0.82 g, 3.6 mmol) and the resulting mixture was stirred for 4 h at rt. The mixture was evaporated in vacuo to yield a residue that was purified via silica gel chromatography eluting with 40percent THF in hexanes to give the title compound as a yellow solid (0.99 g, 89percent). NMR (DMSO-i , 300 MHz): δ 12.82 (s, 1H), 8.42 (s, 1 H), 8.20 (s, 1 H). HPLC retention time: 2.23 minutes. MS ESI (m/z): 324.0, 326.0 (M+H)0 C, Sodium hydride (550 mg, 13.75 mmol)Was added portionwise to a solution of 2-bromo-7-iodo-5H-pyrrolo [2, 3-b] pyrazine (3.00 g, 8.37 mmol)N, N-dimethylformamide (20 mL).After stirring at room temperature for 1.5 h, A solution of methyl iodide (2.2 g, 16.00 mmol) was slowly added dropwise at 0 C, After dripping, The reaction was stirred at room temperature for 5 h.The reaction was quenched with water (50 mL), extracted with ethyl acetate (50 mL x 3)The organic layer was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, concentrated to remove the solvent, The residue was subjected to column chromatography (petroleum ether / ethyl acetate (v / v) = 3/1) to give 2.00 g of a pale yellow solid in 64.2% yield.

Molecular Weight:323.92
XLogP3:2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:322.85551
Monoisotopic Mass:322.85551
Topological Polar Surface Area:41.6
Heavy Atom Count:11
Complexity:157
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes