Trimethylsilylacetylene → 5-Bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine

Temperature

-2.5 °C

To a solution of 3,5-dibromopyrazin-2-amine (125 g, 494 mmol), TEA (207.0 mL, 1483 mmol), and copper (I) iodide (0.941 g, 4.94 mmol) in THF (1255 mL) was added PdCl2(PPh3)2 (3.47 g, 4.94 mmol). The reaction mixture was cooled at about −5-0° C. and a solution of (trimethylsilyl)acetylene (65.0 mL, 470 mmol) in THF (157 mL) was added dropwise over about 15 min. The reaction mixture was stirred at about −5-0° C. for about 1.5 h and then allowed to warm to rt overnight. The reaction mixture was then filtered through a Celite® pad and washed with THF until no further product eluted. The filtrate was concd under reduced pressure to give a brown-orange solid. The solid was triturated and sonicated with warm petroleum ether (b.p. 30-60° C., 400 mL), cooled to rt, collected, washed with petroleum ether (b.p. 30-60° C.; 2×60 mL), and dried to give 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (124 g, 93%, 93% purity) as a brown solid: LC/MS (Table 1, Method b) Rt=2.51 min; MS m/z: 270, 272 (M+H)+.

1. temperatureto warm to rt overnight
2. filtrationThe reaction mixture was then filtered through a Celite® pad
3. washwashed with THF until no further product
4. washeluted
5. customto give a brown-orange solid
6. customThe solid was triturated
7. customsonicated with warm petroleum ether (b.p. 30-60° C., 400 mL)
8. temperaturecooled to rt
9. customcollected
10. washwashed with petroleum ether (b.p. 30-60° C.; 2×60 mL)
11. customdried

ORD record

ord-9f27fbe705df4104a4d3c654e9bc3aa2

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426411B2