反应详情

温度

-10 °C

Lithium bis(trimethylsilyl)amide (800 mL of a 1N solution in THF, 800 mmol) was added dropwise to a cooled (−78° C.) suspension of 1-benzenesulfonyl-5-bromo-2-{[cyanomethyl-(toluene-4-sulfonyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester (154 g, 250 mmol) in dry THF (1.25 L). The reaction mixture was allowed to slowly warm to −10° C. then slowly quenched into cold 1M hydrochloric acid. The layers were separated and the aqueous layer further extracted with THF. The combined organic layer was washed with brine, dried (Na2SO4), filtered and evaporated. The resultant residue was triturated with methanol then acetone and air dried to afford the title compound as a beige solid (77.6 g, 72%). LCMS (Method B): RT=3.83 min, M+H+=429/431. 1H NMR (400 MHz, DMSO-d6): 9.22 (s, 1H), 8.83 (d, J=2.3 Hz, 1H), 8.81 (d, J=2.3 Hz, 1H), 8.19-8.16 (m, 2H), 7.75-7.74 (m, 1H), 7.65-7.59 (m, 2H).

1. temperaturea cooled
2. customthen slowly quenched into cold 1M hydrochloric acid
3. customThe layers were separated
4. extractionthe aqueous layer further extracted with THF
5. washThe combined organic layer was washed with brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. customevaporated
9. customThe resultant residue was triturated with methanol
10. dry with materialacetone and air dried