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

To a solution of sodium hydride (480 mg, 12.00 mmol, 1.10 equiv, 60percent) in tetrahydrofuran (50 mL), a solution of 2, 4-dichloro-7H-pyrrolo[2, 3-d]pyrimidine (2 g, 10.64 mmol, 1.00 equiv) in tetrahydrofuran (50 mL) was slowly added. [00237] To a solution of 2, 4-dichloro-7H-pyrrolo[2, 3-d]pyrimidine (1.5 g, 7.98 mmol) in THF (30 ml) at 0 °C was added sodium hydride (60percent oil suspension, 383 mg, 9.57 mmol) and stirred at 0 °C to r.t. for 20 mins. lodomethane (0.6 ml, 9.57 mmol) was added and stirred at r.t. for 3 h. [00238] The mixture was quenched by addition of saturated ammonium chloride solution (20 mL). EtOAc was then added resulting in formation of a precipitate. The precipitate was filtered and the filtrate extracted with EtOAc (x2). The combined organic fractions were washed with water, dried over Na2S04, filtered and concentrated in vacuo to afford the title compound (1.65 g, 97.2percent) as a yellow powder. [00239] Method A: LC-MS m/z = 201.90, 203.90 [M + H]+; RT = 1.21 min.Step 1 : To a stirred solution of 2, 4-dichloro-7/-/-pyrrolo[2, 3-c]pyrimidine (2 g, 10.638 mmol) in DMF (20 mL) was added 60 percent NaH (0.63 g, 15.957 mmol, 1.5 equiv) at 0 °C and stirred for 30 min at room temperature. Methyl iodide (0.79 mL, 12.765 mol, 1.2 equiv) was added and allowed to stir at room temperature for 3 h. The reaction was quenched with ice water (200 mL) and the precipitated solid was filtered and dried in vacuo to obtain 2, 4-dichloro-7-methyl- 7H-pyrrolo[2, 3-c]pyrimidine as an off white solid (2.06 g, 96 percent). LCMS (ES) m/z = 202.1 , 204.0 [M+H]A solution of2, 4-Dichloro-7H-pyrrolo [2, 3-d] pyrimidine (5.0 g, 26.6 mmol) was dissolved in tetrahydrofuran (50 mL)Triethylamine (4.0 g, 39.5 mmol) was added, Methyl iodide (4.2 g, 29.6 mmol) was added dropwise, After the addition was complete, the temperature was raised to 25 ° C and reacted for 16 hours.After the reaction was completed, the reaction solution was poured into water (100 mL)The precipitated solid was filtered, drying, The product (5.0 g, 93percent yield) was obtained.A 0 °C solution of 2, 4-dichloro-7H-pyrrolo[2, 3-d]pyrimidine (1.00 g, 5.32 mmol) in THF (8 mL) was stirred for 5 mm, then to the solution was added sodium hydroxide (255 mg, 6.38 mmol). The mixture was stirred for further 15 mm, and iodomethane (8.50 g, 53.20 mmol) was added. The mixture was stirred at rt overnight. To the reaction mixture was added H20 (100 mL), and the mixture was extracted with EtOAc (50 mL x 3). The combined organic layers were washed with saturated brine (80 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo dry, and the residue was purified by silica gel column chromatography (PE/EtOAc (v/v) = 10/1) to give the title compound as a white solid (1.00 g, 93 percent).MS (ESI, pos. ion) m/z: 202.95 [M+Hfb.2, 4-Dichloro-7H-pyrrolo[2, 3-d]pyrimidine (1.00 g, 5.32 mmol)Dissolved in THF (8 mL), and the resulting solution was stirred at 0 ° C for 5 min.Then sodium hydride (255 mg, 6.38 mmol) was added thereto.The resulting reaction solution was stirred for 15 minutes.Methyl iodide (8.50 g, 53.20 mmol) was added thereto.The resulting reaction solution was transferred to room temperature and stirred overnight.The reaction was quenched by H2O (EtOAc) (EtOAc)The combined organic phases were washed with brine (80 mL).Dry over anhydrous sodium sulfate, filter, and concentrate the filtrate under reduced pressure.The residue was chromatographed on silica gel ( petroleum ether / ethyl acetate (v/v) = 10/1)Purification to give the title compound as a white solid(1.00g, 93percent).A solution of 2, 4-dichloro-7H-pyrrolo[2, 3-d]pyrimidine (1.00 g, 5.32 mmol) in THF (8 mL) was stirred at 0 °C for 5 mm. Then sodium hydride (255 mg, 6.38 mmol) was added. The resulting mixture was stirred for 15 mm, then iodomethane (8.50 g, 53.20 mmol) was added. The reaction mixture was warmed to rt and stirred overnight. H20 (100 mL) was added to quench the reaction, and the resulting mixture was extracted with EtOAc (50 mL x 3). The combined organic phases were washed with brine (80 mL), dried over anhydrous Na2504, filtered, and the filtrate was concentrated in vacuo. The residue was purified by silica gel chromatograph (PE/EtOAc (v/v) = 10/1) to give the tilte compound as a white solid (1.00 g, 93 percent).MS (ESI, pos. ion) m/z: 203.0 [M+H]tA solution of 2, 4-dichloro-7H-pyrrolo [2, 3-d] pyrimidine (1.00 g, 5.32 mmol) in THF (8 mL) was stirred for 5 min at 0 , then sodium hydride (255 mg, 6.38 mmol) was added. The mixture was stirred for 15 min, and then iodomethane (8.50 g, 53.20 mmol) was added. The resulting mixture was warm to rt and stirred overnight, then the reaction was quenched with HTo a solution of 60percent NaH (750 mg) in dry THF (20 mL), a solution of 18a (1.7 g) in dry THF (50 mL) was slowly added. The resulting solution was stirred at 0 °C for 30 min followed by the addition of MeI (0.79 mL) at 0 °C. The mixture was stirred at room temperature overnight. After the addition of 20 mL water, the solution was extracted with ether (3.x.10 mL) and washed with saturated brine. The organic phase was dried with anhydrous sodium sulfate and filtered. Ether was evaporated in vacuo to yield a crude residue, which was purified by silica gel chromatography (PE/EA= 10/1) to give 18d (1.53 g, yield: 84.1percent). ESI-MS calculated for (CA solution of 2, 4-dichloro-7H-pyrrolo[2, 3-d]pyrimidine (3.00 g, 16.0 mmol) in anhydrous tetrahydrofuran (45 mL) was cooled to 0° C. and treated with a 60percent dispersion of sodium hydride in mineral oil (0.83 g, 20.8 mmol). The reaction was stirred at 0° C. for 20-30 min. The reaction was then treated with iodomethane (3.65 g, 1.6 mL, 25.7 mmol), and the reaction stirred at room temperature overnight. The reaction was diluted with a saturated aqueous ammonium chloride solution (50 mL) and water (50 mL) and was extracted with a 10percent methanol in methylene chloride solution (4×50 mL). The combined organic layers were dried over magnesium sulfate, filtered and rinsed with methylene chloride, and concentrated in vacuo onto Celite®. Flash chromatography (80 g silica gel column, 0-15percent ethyl acetate/hexanes) afforded 2, 4-dichloro-7-methyl-7H-pyrrolo[2, 3-d]pyrimidine as a light yellow solid (2.39 g, 74.1percent). To a solution of 2, 4-dichloro-7H-pyrrolo[2, 3-djpyrimidine 34 (237 mg, 1.26 mmol) in CH3CN (1 mL) was added NaH (33.3 mg, 1.39 mmol) portion- wise at 0 °C. The reaction mixture was stirred at room temperature for 20 mm until gas evolution was ceased. Methyl iodide (86.4 i.il, 1.39 mmol) was added and stirred the reaction mixture for 1 h at room temperature. To the reaction mixture was added water and extracted with ethyl acetate (2 x 30 mL). The combined organic layers were dried over Mg504, and then concentrated under vacuum. The resultant crude residue was purified by silica-gel column chromatography to afford 35 (144 mg, 58percent) as white solid. ‘H-NMR (400 MHz, DMSO-d6) ö 7.76 (d, J = 3.6 Hz, 1H), 6.71 (d, J = 3.6 Hz, 1H), 3.81 (s, 3H); MS: (m/z) [M+Hjb 204.02.A 0 oc solution of 2, 4-dichloro-7 H-pyrrolo[2, 3-d]pyrimidine ( 1.00 g, 5.32 mmol) inTHF (8 mL) was stirred at 0 oc for 5 min. Then sodium hydride (255 mg, 6.38 mmol) was added.The resulting mixture was stirred for 15 min, then iodomethane (8.50 g, 53.20 mmol) was added.The reaction mixture was warmed to rt and stirred overnight. To the reaction mixture was addedwater (60 mL) to quench the reaction, and the resulting mixture was extracted with ethyl acetate(50 mL x 3). The combined organic layers were washed with saturated brine (80 mL), dried overanhydrous sodium sulfate and filtered. The filtrate was concentrated and the residue was purified by silica gel column chromatography (PE/EtOAc (v/v) = 1011) to give the title compound as awhite solid (1.00 g, 93 percent ).MS (ESI, pos. ion) m/z: 202.0[M+Ht.(1 g, 5.318 mmol) and powdered KOH (446 mg, 7.978 mmol) was dissolved in 4 mL anhydrous DMSO. After 1 h at RT, the reaction mixture was quenched with water and the aqueous layer was extracted with EtOAc (2x).The organics were combined, dried (MgSO

Molecular Weight:202.04
XLogP3:2.5
Hydrogen Bond Acceptor Count:2
Exact Mass:200.9860526
Monoisotopic Mass:200.9860526
Topological Polar Surface Area:30.7
Heavy Atom Count:12
Complexity:178
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes