6-Bromo-2,4-dichloro-7-(phenylsulfonyl)-7H-Pyrrolo[2,3-d]pyrimidine synthesis

Yield:1131992-26-1 71%

Reaction Conditions:

Stage #1: 7-(benzenesulfonyl)-2,4-dichloro-pyrrolo[2,3-d]pyrimidinewith lithium diisopropyl amide in tetrahydrofuran at -78 - 0; for 0.5 h;
Stage #2: with 1,2-dibromo-1,1,2,2-tetrachloroethane in tetrahydrofuran at -78; for 2 h;

Steps:

32; 4

A solution of LDA in THF, prepared at 0 ⁰C by addition of n-BuLi (2.5 M in hexanes, 2.5 ml_, 6.378 mmol) to a solution Of Z-Pr₂NH (980 μl_, 6.932 mmol) in 5 mL of anhydrous THF, cooled to -78 ⁰C was treated with a solution of Example 31 (910 mg, 2.773 mmol) in 10 mL THF. After 30 min, the reaction mixture was treated with a solution of 1 ,2-dibromo-tetrachloroethane (2.709 g, 8.319 mmol) in 10 mL THF. After 2 h at -78 ⁰C, the reaction mixture was quenched with sat NH₄CI(aq) (20 mL). The aqueous layer was extracted with EtOAc (2x). Organics were combined, dried (MgSO₄), filtered and the volatiles were removed in vacuo. The residue was purified by flash chromatography (50 g lsolute SiO₂ cartridge, gradient hexanes 100% to hexanes/EtOAc, 4:1 ) to provide the desired product (805 mg, 71 %) as a colourless solid. ¹H NMR (CDCI₃) δ 8.26-8.23 (2H, m), 7.68 (1 H, dt, J = 1.2, 7.6 Hz), 7.60-7.56 (2H, m), 6.81 (1 H, s).

References:

WO2009/37467,2009,A1 Location in patent:Page/Page column 33; 15