N-Tosyl-5-bromo-4,7-diazaindole

To a solution of 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (3.00 g, 11.1 mmol) in DMF (60 mL) at about 0° C. was added NaH (60percent dispersion in mineral oil, 0.577 g, 14.4 mmol) in three portions. After about 15 min, p-toluenesulfonyl chloride (2.75 g, 14.4 mmol) was added and the reaction was allowed to warm slowly to ambient temperature. After about 16 h, the reaction mixture was poured onto ice-cold water (120 mL) and the precipitate was collected by vacuum filtration. The crude solid was dissolved in DCM (15 mL) and purified by silica gel chromatography eluting with DCM. The product-containing fractions were concentrated under reduced pressure to give 2-bromo-5-tosyl-5H-pyrrolo[2, 3-b]pyrazine (2.16 g, 52percent): LC/MS (Table 2, Method d) RTo a 0 oc solution of 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (1.22 g, 4.52 mmol) in anhydrous DMF (10 mL) was added sodium hydride (253 mg, 6.33 mmol, 60 percent).The mixture was stirred at 0 oc for 15 min, then paratoluensulfonyl chloride (865 mg, 4.51mmol) was added into the mixture. The resulting mixture was warmed to rt and stirred for 3 h.To the reaction mixture was added ice-water (40 mL) to quench the reaction, and the resultingmixture was extracted with ethyl acetate (30 mL x 3). The combined organic layers were washedwith saturated brine (60 mL), dried over anhydrous sodium sulfate and filtered. The filtrate wasconcentrated in vacuo and the residue was purified by silica gel column chromatography(PE/EtOAc (v/v) = 1011) to give the title compound as a yellow solid (624 mg, 39.2 percent).Step B: 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine to 2-bromo-5-tosyl-5H-pyrrolo[2, 3-b]pyrazine [0184] To a solution of 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (3.00 g, 11.1 mmol) in DMF (60 mL) at about 0° C. is added NaH (60percent dispersion in mineral oil, 0.577 g, 14.4 mmol) in three portions. After about 15 min, p-toluenesulfonyl chloride (2.75 g, 14.4 mmol) is added and the reaction is allowed to warm slowly to ambient temperature. After about 16 h, the reaction mixture is poured onto ice-cold water (120 mL) and the precipitate is collected by vacuum filtration. The crude solid is dissolved in DCM (15 mL) and purified by silica gel chromatography eluting with DCM to give 2-bromo-5-tosyl-5H-pyrrolo[2, 3-b]pyrazine (2.16 g, 52percent): LC/MS (Table 1, Method c) RA solution of 2-bromo-5H-pyrrolo[2, 3-b]pyrazine (78.0 g, 394 mmol, Ark Pharm) in anhydrous DMF (272 mL) was added drop-wise over about 60 min to a stirred suspension of NaH (12.8 g, 532 mmol) in anhydrous DMF (543 mL) at about 0-5° C. The brown reaction solution was stirred for about 30 min at about 0-5° C. then a solution of p-toluenesulfonyl chloride (94.0 g, 492 mmol) in anhydrous DMF (272 mL) was added drop-wise over about 60 min at about 0-5° C. The reaction mixture was stirred at about 0-5° C. for about 1 h then allowed to warm to ambient temperature and stirred for about 18 h at ambient temperature. The reaction mixture was poured slowly into ice water (6 L), followed by the addition of aqueous 2.5 N NaOH (50.0 mL, 125 mmol). The precipitate was collected by filtration and stirred with cold water (3.x.200 mL). The solid was collected by filtration and dried to constant weight in a vacuum oven at about 55° C. to yield 2-bromo-5-tosyl-5H-pyrrolo[2, 3-b]pyrazine (134.6 g, 97percent) as a pale beige solid: LC/MS (Table 2, Method d) R2-bromo-5H-pyrrolo [2, 3-b] pyrazine (10 g, 50.5 mmol)Of tetrahydrofuran (150 mL)Was added sodium hydride (60percent, 3.1 g, 78 mmol)The mixture was stirred at room temperature for 1 hour, P-toluenesulfonyl chloride (12.6 g, 65.4 mmol) was added under ice-Continue to stir at room temperature, Diluted with water (100 mL)Dichloromethane extraction (100 mL x 3), Dried over anhydrous sodium sulfate, Concentrated column chromatography (petroleum ether / ethyl acetate (v / v) = 8/1)To give 14.1 g of a pale yellow flocculent solid in a yield of 79.3percent.

Molecular Weight:352.21
XLogP3:2.9
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:350.96771
Monoisotopic Mass:350.96771
Topological Polar Surface Area:73.2
Heavy Atom Count:20
Complexity:445
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes