4,5-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

General procedure: To a solution of readily available 3a (20mmol) in N, N-dimethylformamide (DMF) (15mL) was added NCS/NBS (21mmol) and the reaction mixture was stirred at room temperature for 72h. Then ice water (150mL) was poured into the mixture, the precipitate was filtered, washed with water (3×100mL), and dried to give 3b and 3c.Dissolve 4-chloro-pyrrolo[2, 3-d]pyrimidine (20 mmol) in DMF (6 mL), add NBS or NCS (21 mmol) in portions on ice bath, react at room temperature for 12 h, and pour the reaction mixture into 80 mL of ice. In the water, a large number of off-white solids precipitated and were filtered. The filter cake was washed with 15 mL of water and dried to give Intermediate 2. 4, 5-dichloro-pyrrolo[2, 3-d]pyrimidine (2a) Gray solid, yield 95percent3H, m), 2.4 (3H, s), 1.31 (3H, J=6.8 Hz, d); MS (ES+) [M+H]PREPARATION 7; 4, 5-dichloro-7H-pyrrolor2, 3-dlpyrimidineN-Chlorosuccinimide (4.78 g, 35.81 mmol) was added portionwise to a stirred suspension of 4-chloro-7H-pyrrolo[2, 3-d]pyrimidine (5g, 32.56 mmol) in DCM, dry (125ml) at room temperature. The resulting suspension was stirred for 1 hour then heated to reflux for 5 hours, then allowed to cool down and left to stir at room temperature overnight. The reaction mixture was evaporated and suspended in water (50 mL). The suspension was filtered giving crude product as a grey solid. The solid was suspended in hot methnol and filtered. The solid was then suspended in hot ethyl acetate and filtered to give 4, 5- dichloro-7H-pyrrolo[2, 3-d]pyrimidine (4.87 g, 80 percent) as a grey solid. IH NMR (400.13 MHz, DMSO-d6) δ 7.91 (IH, s), 8.64 (IH, s), 12.87 (IH, s) MS m/e MHPREPARATION I4, 5-dichloro-7H-pyrrolor2, 3-dlpyrimidine; N-Chlorosuccinimide (4.78 g, 35.81 mmol) was added portionwise to a stirred suspension of 4-chloro-7H-pyrrolo[2, 3-d]pyrimidine (5g, 32.56 mmol) in DCM, dry (125ml) at room temperature. The resulting suspension was stirred for 1 hour then heated to reflux for 5 hours, then allowed to cool down and left to stir at room temperature overnight. The reaction mixture was evaporated and suspended in water (50 mL). The suspension was filtered giving crude product as a grey solid. The solid was suspended in hot methnol and filtered. The solid was then suspended in hot ethyl acetate and filtered to give 4, 5- dichloro-7H-pyrrolo[2, 3-d]pyrimidine (4.87 g, 80 percent) as a grey solid. IH NMR (400.13 MHz, DMSO-d6) δ 7.91 (IH, s), 8.64 (IH, s), 12.87 (IH, s) MS m/e MHMETHOD I A. Preparation of 4, 5-dichloro-7H-pyrrolo[2, 3-d]pyrimidine; Following the procedure in Pdulo, J. S.; Saxena, N. K.; Nassiri, M. R.; Turk, S. R.; Drach, J. C.; Townsend, L. B. J. Med. Chem. 31:2086 (1988), 4-chloro-5-methyl-7H-pyrrolo[2, 3-d]pyrimidine (Example 1A, 20. g, 0.13 mol) was suspended in anhydrous dichloromethane (500 mL), followed by addition of N-chlorosuccinimide (20.8 g, 0.160 mol). The reaction mixture was refluxed at 43° C. for 8 hours. The reaction was cooled down, and the white solid was filtered, washed with dichloromethane (300 mL), and dried to give 4, 5-dichloro-7H-pyrrolo[2, 3-d]pyrimidine (20 g, 83percent)

Molecular Weight:188.01
XLogP3:2.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:186.9704025
Monoisotopic Mass:186.9704025
Topological Polar Surface Area:41.6
Heavy Atom Count:11
Complexity:155
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes