4-Chloro-5-iodo-7H-pyrrol[2,3-d]pyrimidine

Step 1.To a solution of 4-chloro-7H-pyrro]o[2, 3-d]pyrimidine (8.0 g , 52.32 mmol, 1.0 eq) in DMF (40 raL), NiS ( 15.7g , 57.55 mmol, 1.1 eq) was added at 0° C. The reaction mixture was stirred overnight at room temperature. Water (40 rnL) was added to the reaction mixture, extracted with EtOAc. The organic layer was dried over NaStep 1To a solution of 4-chloro-7H-pyrrolo[2, 3-d]pyrimidine (8.0 g , 52.32 mmol, 1.0 eq) in DMF (40 mL), NIS ( 15.7g , 57.55 mmol, 3.1 eq) was added at 0° C. The reaction mixture was stirred overnight at room temperature. Water (40 mL) was added to the reaction mixture, extracted with EtOAc. The organic layer was dried over NaStep 1. To a solution of 4-chloro-7H-pyrrolo[2, 3-d]pyrimidine (8.0 g, 52.32 mmol, 1.0 eq) in DMF (40 mL), NIS (15.7g, 57.55 mmol, 1.1 eq) was added at 0° C. The reaction mixture was stirred overnight at room temperature. Water (40 mL) was added to the reaction mixture, extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated under vacuum to give 4-chloro-5-iodo-7H-pyrrolo[2, 3-d]pyrimidine (14.6 g, 100 percent in yield).Step 1 4-chloro-7H-pyrrolo[2, 3-d]pyrimidine (8.0 g, 52.32 mmol, 1.0 eq) was dissolved in DMF (40 mL), NIS (15.7 g, 57.55 mmol, 1.1 eq) was added at 0°C, stirred overnight at room temperature, 200 mL of saturated NaA solution of 4-chloro-7H-pyrrolo[2, 3-d]pyrimidine (201) (500 mg, 3.25 mmol) and NIS (805 mg, 1.1 eq, 3.6 mmol) in DMF (1 mL) was stirred at room temperature for 1 h. The mixture was concentrated in vacuo, then water (10 mL) was added. The resulting solid was collected by filtration. Then dried in vacuo to afford the desired product, 4-chloro-5-iodo-7H-pyrrolo[2, 3-d]pyrimidine (202) (900 mg, 99percent yield) as a off-white solid. ESI-MS m/z: 277.85 [M−H]To a dry 250 mL round bottomed flask under argon was added 1.8 g (11.9 mmol) of 4-chloro-7H-pyrrolo[2, 3-d]pyrimidine and 3.0 g of N-iodosuccinamide (13.1 mmol). The solids were dried under high vacuum for 5 hours and the flask was refilled with argon. Dry DMF (100 mL) was added and the solution was stirred in the dark for 20 hours. The reaction was quenched with methanol and concentrated. The residue was then diluted with 150 mL of dichloromethane and washed with water (200 mL), saturated aqueous sodium sulfite (200 mL), and brine (100 mL). The organic layers were dried over MgSO4-Chloro-5-iodo-7H-pyrrolo[2, 3]pyrimidine 4-Chloro-7H-pyrrolo[2, 3-d]pyrimidine (1.8 g 11.9 mmol) and N- iodosuccinamide (3g, 13.1 mmol) were mixed in a round bottomed flask. The flask was dried under high vacuum for 5 h and then back-filled with argon. To this mixture, dry DMF (100 mL) was added and the resulting mixture was stirred in the dark for 20 h. The reaction was quenched with methanol and concentrated in vacuo. The residue was diluted with 150 mL of DCM and washed with water (200 mL), saturated aqueous sodium sulfite (200 mL), and brine (100 mL). The organic layer was dried over MgSO4-Chloro-7H-pyrrolo[2, 3-d]pyrimidine (1.8 g 11.9 mmol) and Niodosuccinamide (3g, 13.1 mmol) were mixed in a round bottomed flask. The flask was dried under high vacuum for 5 h and then back-filled with argon. To this mixture, dryDMF (100 mL) was added and the resulting mixture was stirred in the dark for 20 h. The reaction was quenched with methanol and concentrated in vacuo. The residue was diluted with 150 mL of DCM and washed with water (200 mL), saturated aqueous sodium sulfite (200 mL), and brine (100 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash columnchromatography on silica gel (50percent ethyl acetate / hexanes) to afford the desired product (3.1 g, 95percent yield) as a white solid. ESI-MS m/z: 279.5 [M + H].To a stirred solution of 4-chloro-7H-pyrrolo[2, 3-d]pyrimidine 41a (7.19 g, 46.8 mmol) in 70 mL of DMF was added N-iodosuccinimide (11.06 g, 49.2 mmol). The solution was stirred in the dark for 18 h at rt before being poured into 100 mL of H2O. The resulting tan precipitate was collected by suction filtration and dried under high vacuum to afford iodide 41b (11.8 g, 90percent) as a tan solid.Preparation of 2-(2'-methyl-β-D-ribofuanosyl)-2, 6-dihydro-2, 3, 5, 6-tetraaza-benzo[cd]azulen-7-one (Compound 301); Step 1; 4-Chloro-7H-pyrrolo[2, 3-d]pyrimidine 10.75 g (70 mmol) and N-iodosuccinimide (16.8 g, 75 mmol) were dissolved in 400 mL of dry DMF and left at ambient temperature in the darkness over night. The solvent was evaporated. The yellow residue was suspended in hot 10percent solution of NaTo a solution of 4-chloro-7H-pyrrolo[2, 3-D]pyrimidineA mixture of 249 4-chloro-7H-pyrrolo[2, 3-d]pyrimidine (500 g, 3255.84 mmol) and 250 NIS (805.74 g, 3581.43 mmol) in 21 DMF (3.3 L) was stirred at rt for 3 hrs. The mixture was poured into ice water (20 L) and resulting solid was filtered, washed with saturated sodium thiosulphate solution (4×2.5 L), water (4×2.5 L) and dried under vacuum to afford the 237 title compound as an off white solid (780 g, 85.8percent). N, N-Dimethylformamide (DMF) (47mL) was added to a mixture of 56 4-chloro-7H-pyrrolo[2, 3-d]pyrimidine (4.60g, 29.8mmol) and 57 N-iodosuccinimide (6.82g, 30.3mmol) under a nitrogen atmosphere. The solution was stirred at 22°C for 2.5h before the mixture was poured into ice water (150mL). The precipitate was filtered, washed with water and n-pentane and dried to give 7.05g (25.2mmol, 85percent) of 12 1 as a pale brown powder; mp. 187–188°C (dec.) (lit [39]. 196–199°C), RScheme 1General Synthesis of 5-Aryl pyπOlor2, 3-d1pyrimidine CompoundsP X, Y = HPreparation 109; 4-Chloro-5-iodo-7H-pyrrolo|METHOD P To a vigorously stirred solution of 11 (1.0 g; 6.51 itimol) in CHTake a 250 mL two-necked flask, add compound 5 (5 g, 33 mmol), argon, Anhydrous DMF solution was added slowly and NIS (8.1 g, 36 mmol, 1.1 equiv.) In anhydrous DMF was added slowly and stirred at room temperature for 3 h. Add saturated sodium thiosulfate solution(50 mL). The EA (100 mL) was added, the organic phase was collected, washed with saturated brine, extracted, dried over anhydrous sodium sulfate, (PE: EA = 4: 1) to give 7.4 g of product as a white solid in 82percent yield.(e) 4-Chloro-7H-pyrrolo[2, 3-d]pyrimidine 10.75 g (70 mmol) and N-iodosuccinimide (16.8 g, 75 mmol) were dissolved in 400 ml of dry DMF and left at ambient temperature in the darkness over night. The solvent was evaporated. The yellow residue was suspended in hot 10percent solution of NaCompound 13a (5.0 g, 32.56 mmol, 1.00 equiv) was taken up in DMF 60 mL. and to the resulting solution was added N-iodosuccinimide (7.3 g, 32.45 mmol, 1.00 equiv) in portions at room temperature. The resulting reaction was allowed to stir for 2 hours at room temperature, and then was concentrated in vacuo. The resulting residue was purified using flash column chromatography on silica gel and eluted with ethyl acetate/petroleum ether (1:3) to provide 6.7 g (74percent) of compound 13b as a white solid.Step 1: 4-chloro-5-iodo-7H-pyrrolo[2, 3-d]pyrimidine A mixture of 4-chloro-7H-pyrrolo[2, 3-d]pyrimidine (3.0 g, 20 mmol) and NIS (4.9 g, 20.1 mmol) in DMF (100 mL) was stirred in darkness at room temperature overnight. Then the mixture was concentrated in vacuo. The residue was treated with 10percent NaSynthesis of 7-(2-nitrobenzyloxy)methyl-7-deaza-2′-deoxyadenosine-5′-triphosphateStep 1 4-Chloro-7H-pyrrolo[2, 3-d]pyrimidine (2 g, 13.02 mmol) was charged in DCM (60 mL) and was added N-iodosuccinimide (3.80g, 16.92 mmol). To this reaction mixture was added DMF (6 mL) and the reaction mixture was stuffed at RT for 1 h. The progress of reaction was monitored by TLC and NMR. After completion of reaction, the solid obtained was filtered off and washed with pentane (30 mL). The solid obtained was dried under vacuum to get 4-chloro-5-iodo-7H-pyrrolo [2, 3-d] pyrimidine (2.8 g).Step 1:4-Chloro-7H-pyrrolo[2, 3-d]pyrimidine 10.75 g (70 mmol) and N-iodosuccinimide (16.8 g, 75 mmol) were dissolved in 400 mL of dry DMF and left at ambient temperature in the darkness over night. The solvent was evaporated. The yellow residue was suspended in hot 10percent solution of Na

Molecular Weight:279.46
XLogP3:2.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:278.90602
Monoisotopic Mass:278.90602
Topological Polar Surface Area:41.6
Heavy Atom Count:11
Complexity:157
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes