2,4-Dichloro-7-tosyl-7H-pyrrolo[2,3-d]pyriMidine

Intermediate 92, 4-Dichloro-7-[(4-methylphenyl)sulfonyll-7H-pyrrolo[2, 3-(i]pyrimidine2, 4-Dichloro-7H-pyrrolo[2, 3-d]pyrimidine (1.00 g, 5.32 mmol), 4-methylbenzene-l-sulfonyl chloride (1.115 g, 5.85 mmol) and tetra-butylammonium hydrogen sulfate (0.090 g, 0.27 mmol) were dissolved in DCM (20 mL) at r.t., and NaOH (50percent aq., 1 mL) was added. The reaction mixture stirred at room temperature for 30 minutes. After completion of the reaction as indicated 103496-1Pby TLC, the reaction mixture diluted with HEXAMPLE 23-((3No., 4No.)-4-Methyl-3-(dA stirred solution of S-1 (2.00 g, 10.7 mmol) in CHIn a flask 2, 4-dichloro-7H-pyrrolo[2, 3-d]pyrimidine (1.0 g, 5.3 mmol) in DMF (30 rnL) was added NaH (60percent in mineral oil, 0.21 g, 5.3 mmol). After stirring 5 min at room temperature the reaction mixture was added tosyl chloride (1.0 g, 5.3 mmol) and stirred 1 h at room temperature. The reaction mixture was diluted with HTo a solution of 2, 4-dichloro-7H-pyrrolo[2, 3-J]pyrimidine (1.0 g, 5.3 mmol) in DMF (30 mL) was added NaH (60percent in mineral oil, 0.21 g, 5.3 mmol). The mixture was stirred for 5 min at room temperature and added tosyl chloride (1.0 g, 5.3 mmol). The mixture was stirred for 1 h at room temperature, diluted with HIn the ice bath conditions, A solution of 2, 4-dichloro-7H-pyrrole [2, 3-d] pyrimidine 1.0 gWas dissolved in 50 mL of dichloromethane, To the above mixed solution, 1.06 g of p-toluenesulfonyl chloride was added slowly, Triethylamine 1.08 g, N, N-dimethylpyridin-4-amine, 0.019 g, The mixed solution was stirred at room temperature for 5 h, After the reaction is complete, To the above solution was poured into 150 mL, the organic phase was washed with water, Citric acid aqueous solution and brine solution were washed three times each. The organic phase was dried with anhydrous magnesium sulfate overnight, and the solvent was evaporated under reduced pressure to obtain crude product.Recrystallization from petroleum ether gave 1.6 g of pure white product.Yield 89percent.To a solution of 2, 4-dichloro-7H-pyrrolo[2, 3-d]pyrimidine (500 mg, 2.66 mmol) in DMF (5 mL) was added NaH (120 mg, 2.93 mmol, 60percent) at 0 °C, and the mixture was stirred at this temperature for 30 mm. Then paratoluensulfonyl chloride (608 mg, 3.19 mmol) was added to the mixture, and the resulting mixture was stirred at rt overnight. To the reaction mixture was added water (50 mL) to quench the reaction, and the resulting mixture was partitioned. The aqueous layer was extracted with ethyl acetate (50 mL x 2). The combined organic layers were washed with saturated brine (80 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (PE/EtOAc (v/v) = 10/1) to give the title compound as a yellow solid (780 mg, 86 percent).MS (ESI, pos. ion) m/z: 343.90 [M+H]+1H NMR (400 MHz, CDC13) (ppm): 8.13 (d, J = 8.3 Hz, 2H), 7.77 (d, J = 4.0 Hz, 1H), 7.38 (d, J = 8.2 Hz, 2H), 6.70 (d, J = 4.0 Hz, 1H), 2.45 (s, 3H).To a solution of 2, 4-dichloro-7Hpyrrolo[2, 3-d]pyrimidine (4.5 g, 23.93 mmol) in DMF (140 mL) was added NaH (0.957g, 23.93 mmol). After stirring for 5 min at room temperature, 4-methylbenzene-1-sulfonyl chloride (4.56 g, 23.93 mmol) was added and the reaction mixture was stirred at room temperature for 1 hour. The mixture was diluted with water (450 mL) and filtered. The solid was washed with water (90 mL) and dried to give the title compound 1a (7 g, 84 percent yield) as a white solid. LCMS: 342 [M+H]+.After 2, 4-dicWoro-7H-pyrrolo[2, 3-d]pyrimidine (3.0 g, 16.0 mmol) was dissolved in acetone (20.0 mL), 4- methylbenzenesulfonyl chloride (4.6 g, 23.9 mmol) was added thereto. After cooling to 0 °C, 2 M sodium hydroxide solution (12.0 mL) was slowly added dropwise and then stirred at room temperature for 2 hours. The organic layer was isolated, treated with magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was isolated by column chromatography to obtain a title compound (2.9 g, yield: 80.0percent). To a suspension of 2, 4-dichloro-7H-pyrrolo[2, 3-d] pyrimidine (l g, 0.005 mol) and toluene sulfonylchloride (1.3gm, 0.007) in 10 ml acetone cooled to about 0-5 °C , a solution of sodium hydroxide in water (0.32gm in 4ml water) was added slowly at about 0-5 °C .The temperature of the reaction mass was raised to 25-30 °C and stirred for 2-3 hrs. The progress of the reaction was monitored by TLC. After completion of the reaction the reaction mass was filtered and washed with a mixture of acetone and water. The solid was dried under vacuum at about 50-55 °C for about 10 hrs to afford 1.5 gm of 2, 4-dichloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2, 3- d]pyrimidine as yellow colored solid. (HPLC purity >98.0percent)REFERENCE fR)-2-Choro-4-[3-(Λf, Wdimethy[amino)pyrrolidin-1-yl]-7-[(4-toiLfy.)suifony.- pyrτolo[2, 3-d]pyrimidine a) 2, 4-Dichloro-7-[(4-toiuyl)suJfonyI]-pyrro[o[2

Molecular Weight:342.2
XLogP3:4.1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:340.9792531
Monoisotopic Mass:340.9792531
Topological Polar Surface Area:73.2
Heavy Atom Count:21
Complexity:476
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes