5-Bromo-4-chloro-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidine

To a solution of 5-Bromo-4-chloro-7H-pyrrolo [2, 3-d] pyrimidine (3. 0g, 13 mmol) in DMF (40 mL) at 0 °C was added NaH (60percent w/w in mineral oil, 720 mg, 18.1 mmol) and the mixture stirred at 0 °C under N2 for 30 minutes. Then PhS02Cl (1.7g, 13 mmol) was added and the reaction stirred at room temperature for 2 hours, after which H20 (200 mL) was added, causing precipitation. The precipitate was collected by filtration and dried under vacuum to give 7-Benzenesulfonyl-5-bromo-4-chloro-7H-pyrrolo [2, 3-d] pyrimidine-(4. 9g, 100percent.)'H NMR (DMSO-d6, 400 MHz) No. 8.85 (1H, s), 8.45 (1H, s), 8.19 (2H, d, J8. 7 Hz), 7.81 (1H, t, J7. 4 Hz), 7.70 (2H, t, J 7. 8 Hz.)METHOD L; 7-Benzenesulfonyl-5-bromo-4-chloro-7H-pyrrolo[2, 3-d]pyrimidine; [0192] To a slurry of the product from Method K (4.1 g/0.018 mol) in DMF (15 mL) and cooled to 0[deg.] C. was added 1.0 g (0.025 mol) of 60percent sodium hydride in mineral oil and the resulting mixture stirred at 0[deg.] C. for 15 minutes. Benzenesulfonyl chloride (3.2 g/0.018 mol) was added, the reaction mixture warmed to room temperature and stirred for 2 hours. Water was then added (15 mL) and the resulting solid removed by filtration and dried in vacuo affording 5.9 grams (89percent) of the title compound.B. Preparation of 5-bromo-4-chloro-7-(phenylsulfonyl)-7H-pyrrolo[2, 3-d]pyrimidine. To a slurry of 5-bromo-4-chloro-7H-pyrrolo[2, 3-d]pyrimidine from step A (1.17 g, 5 mmol) in DMF (10 ml) at 0° C., was added NaH (60percent in mineral oil, 0.28 g, 7 mmol). After stirring 15 min., benzensulfonyl chloride (0.64 ml, 5 mmol) was added. The reaction mixture was warmed to room temperature and stirred for 2 hours, resulting in precipitation of a white solid. More DMF (5 ml) was added, and the reaction was quenched with 10 ml of water. The solid was collected by filtration and dried in vacuum to afford 5-bromo-4-chloro-7-(phenylsulfonyl)-7H-pyrrolo[2, 3-d]pyrimidine (1.62 g, 4.35 mmol, 87percent) as a white solid, which was carried on without further purification. MS (ES+) [M+H]N-4-piperidinylbenzamide (1.316 g, 6.44 mmol) and DIPEA (1.87 mL, 10.73 mmol) in NuMuRho (8 mL) was heated in the microwave at 150 C for 20 minutes. The mixture was partitioned between EtOAc (70 mL) and water (60 mL), and the organic phase washed with water (2 x 60 mL) and brine (50 mL) before it was dried (MgS04), filtered and the solvent removed in vacuo. The crude material was purified by silica chromatography, eluting 0-5 % MeOH in DCM to give D6 as a pure white solid (338 mg), 1H NMR (CDC13) delta 8.47 (1H, s), 8.23 (2H, dd), 7.75 (2H, dd), 7.63 (2H, m), 7.52 (3H, m), 6.95 (2H, m), 6.02 (1H, d), 4.28 (1H, m), 4.24 (2H, dt), 3.22 (2H, dt), 2.19 (2H, m), 1.73 (2H, m), MS(ES+) 540[M(C24H2279BrN503S)+H]+.

Molecular Weight:372.63
XLogP3:3.5
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:370.91309
Monoisotopic Mass:370.91309
Topological Polar Surface Area:73.2
Heavy Atom Count:20
Complexity:452
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes