2-Amino-4-chloropyrrolo[2,3-d]pyrimidine

White Crystalline Solid

The G005 (10. 0g, 66. 6mmol) was added to lOOmLPOCl3, refluxed for 2h, the solvent spin After cooling to room temperature, the reaction was added to 120mL of ice water, and the solid was filtered, and the filtrate was washed with aqueous ammonia solution to pH = 2, and the ice bath and the precipitate As 2h after filtration, the solid was filtered and washed first with ice water 10mL, 30mL second ice was washed with ether, was drained after 8. 7g, 78percent yield .Phosphorus oxychloride (32 mL) and 7-deazaguanine (0.80 g, 5.33 mmol) were heated under reflux for 1hr 30min. After cooling the mixture was concentrated under high vacuum. Later some ice was cautiously added and then some water. The mixture was then neutralized with sodium hydrogen carbonate salt. The precipitated solid was filtered off and dried to yield (0.57 g, 3.4 mmol, 64percent) of the chlorinated final material. 2-Amino-3H, 4H, 7H-pyrrolo[2, 3-d]pyrimidin-4-one (500 mg, 3.33 mmol, 1.00 equiv) was dissolved in phosphorus oxychloride (3 mL). The resulting solution was stirred for 5 h at 110°C. The reaction was quenched by the addition of 20 mL of water/ice. The resulting solution was extracted with 3x50 mL of dichloromethane and the organic layers were combined and concentrated under vacuum. The residue was purified by silica gel column chromatography with dichloromethane/methanol (1 : 10). This resulted in 0.3 g (53percent) of 4-chloro-7H-pyrrolo[2, 3-d]pyrimidin-2-amine as a light yellow solid.Step A2:4-Chloro-7H-pyrrolo[2, 3-d]pyrimidin-2-ylamine. To a solution of 2-amino-3, 7-dihydro- pyrrolo[2, 3-d]pyrimidin-4-one (5.00 g, 33.3 mmol), dimethylaniline (4.22 mL, 41.0 mmol) and benzyltriethylammonium chloride (15.2 g, 66.6 mmol) in acetonitrile (25 mL) at room temperature under argon was added POClStep 1. Creation of the heterocycle (FIG. 3). To a solution of 2, 4-diamino-6-hydroxypyrimidine (1, 25.2 g) in DMF (480 mL) and water (80 mL) was added sodium acetate (27.2 g). The resulting yellow solution was stirred for 1 h. To the solution was added chloroacetaldehyde (50percent solution, 25.4 mL) and the mixture was stirred at rt for 2 days. The volatiles were removed in vacuo and the residue was mixed with methanol (70 mL) and stored at rt overnight. The resulting solid was filtered. The solid was mixed with methanol (150 mL) and heated at 60° C. for 10 min and cooled to rt overnight. The resulting solid was filtered and dried. The yield of 2 was 15 g to 19 g. (0032) A mixture of 7-deazaguanine (14.2 g) and dimethylaniline (6 mL) in POClTo a round-bottomed flask were added 26 (3 g, 19.9 mmol) of and three drops of N, N'-dimethyl aniline. The mixture was suspended on phosphorus oxychloride (250 mL). The reaction was continued at reflux for 4 h. After cooling to room temperature, the solvent was evaporated under reduced pressure and the residue was treated with ice water (20 mL) in an ice bath. The pH of the suspension was adjusted to 7 with concentrated ammonium hydroxide solution. The precipitate was filtered, air-dried and then dissolved in methanol. Silica gel (6 g) was added to the solution which was then evaporated to dryness to form a plug. The silica gel plug obtained was loaded onto a silica gel column and eluted with 2percent methanol in chloroform. Fractions corresponding to the product (TLC) were pooled and evaporated to dryness under reduced pressure to afford 27 (10percent) as a sparkling white solid: mp 215-216 °C; TLC RCompound 21 3 (2.95g; 0.02mol) was suspended in 24 POCl

Molecular Weight:168.58
XLogP3:1.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Exact Mass:168.0202739
Monoisotopic Mass:168.0202739
Topological Polar Surface Area:67.6
Heavy Atom Count:11
Complexity:154
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes