With N-Bromosuccinimide In dichloromethane at 0 - 25℃; for 2 h;
Example 1 5-(1H-1,3-Benzodiazol-2-yl)-7-methyl-N-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine[0122]STEP 1: 5-Bromo-4-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine [Chem. 3]To a stirred solution of 4-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine (WO2005/095357, 6.02 g, 35.9 mmol) in dichloromethane (120 mL) was added N-bromosuccinimide (7.67 g, 43.1 mmol) at 0 oC. The resulting mixture was stirred at room temperature for 2 hrs. The reaction mixture was quenched with saturated sodium bicarbonate aqueous solution (200 mL), and extracted with dichloromethane (200 mL). The organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography (dichloromethane/ethyl acetate=10/1) to give the title compound (8.27 g, 93percent) as a white solid.;LCMS (Method A) m/z: M+1 247.9; tR = 2.70 min.
86%
With N-Bromosuccinimide In dichloromethane at 15 - 23℃; for 3 h;
Add N-bromosuccinimide (418 g, 2.35 mol) portionwise over 20 min at 15 °C to a solution of 4-chloro-7-methyl-pyrrolo[2,3-d]pyrimidine (355 g, 2.12 mol) indichloromethane (3.19 L), and stir at 23 °C for 3 h. After this time, filter, wash with H20 (5.32 L), and dry to give the title compound (448 g, 86percent) as a white solid. ES/MS m/z (35C1,79Br) 245.9 (M+H).
STEP 2: 4-Chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid [Chem. 4]To a stirred solution of <strong>[1266343-30-9]5-bromo-4-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine</strong> (STEP 1, 8.20 g, 33.3 mmol) in tetrahydrofuran (120 mL) was added 1.59 M n-butyllithium in hexane solution (25.1 mL, 39.9 mmol) slowly at -78 oC. After stirring at -78 oC for 1 hr, solid CO2 was added to the mixture. The resulting was warmed to room temperature gradually, and quenched with 1M HCl aqueous solution (200 mL). The mixture was extracted with dichloromethane/methanol (10/1, 200 mLx4), and the combined organic fraction was dried over magnesium sulfate. After removal of the solvent by evaporation, the residue was triturated with ethyl acetate (100 mL) and collected by filtration to give the title compound (6.11 g, 87%) as an off-white solid.;LCMS (Method A) m/z: M+1 212.0; tR = 1.30 min.
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