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

[4-CHLORO-5-BROMO-7H-PYRROLO] [2, 3-d] pyrimidine 2 (0.6 g, 2.60 [MMOL)] was dissolved in 30 mL THF (dry), then [COOLED TO-78°C] before adding 4.10 mL nBuLi (1.6 [M] in hexane) dropwise over a period of 10 minutes. The mixture was stirred for 20 minutes [AT-78°C] before adding 3.38 mmol N- fluorobenzene sulfonimide (NFSI) (1.065 g in 6.5 mL dry THF) dropwise over a period of 15 minutes. The mixture was warmed to room temperature overnight, quenched with 2 mL water, and then evaporated to dryness. The crude preparation obtained was partitioned between ethyl acetate (EtOAc) and a saturated solution of ammonium chloride (40 mL/20 mL) then the aqueous layer was extracted with 20 mL of EtOAc and the combined organic layers were washed with 20 mL water. The organic layer was dried with [MGS04, ] filtered, and the solvent was evaporated. The crude was purified on silica-gel (silica-gel solid deposit in [MEOH)] with 4percent MeOH/CH2CI2 to provide the title compound (0.36 g, [71 percent YIELD)] ; [1H] NMR (DMSO) : [8] 7.70 (s, 1H) ; 8.62 (s, [1H)] ; 12.25 (s, NH)4-CHLORO-7H-PYRROLOPYRIMIDINE 1 (5 g, 32.7 mmol) and Selectfluor (17.35 g, 49 mmol) were placed in a round bottom flask, followed by the addition of dry acetonitrile (250 mL) and ACOH (50 mL). The solution was then heated at 70 °C for 14 h under N2. After cooling to room temperature, the solvent was removed in vacuo and co-evaporated with toluene (50 mL x 2). The solid was dissolved in a mixture of DCM : EtOAc (1: 1) and filtered through a pad of silica gel which was thoroughly washed. The combined washings were evaporated. And the crude product was then subjected to column chromatography with DCM: EtOAc (4: 1) to give 3.3 g (59percent yield) of 2 as a white SOLID. 1H NMR (DMSO-d6) 8 7.73 (s, 1H), 8.64 (s, 1H), 12.5 (br s, 1H); 13C NMR (DMSO-d6) 8 105.3 (d, J= 14.3 Hz), 111.0 (d, J= 25. 5 Hz), 139.6 (d, J= 244.5 Hz), 146.7 (d, J= 1.5 Hz), 148. 5 (d, J= 3.8 Hz), 151.0 ; 19F NMR (DMSO-D6) 8-170. 7 ( d, J= 1.6 Hz): Mass spectroscopy (MS) measured for C6H3C1FN3 (M+H): 172.0, observed: 172.0.To a solution of 4-chloro-7H-pyrrolo[2, 3-d]pyrimidine (2.00 g) in acetonitrile (100 mL) were added acetic acid (20 mL) and N-fluoro-N'-(chloromethyl)triethylenediamine bis(tetrafluoroborate) (6.92 g), and the mixture was stirred under nitrogen atmosphere at 70°C for 18 hours. The reaction mixture was cooled to room temperature, and then concentrated under reduced pressure. To the residue was added methylene chloride/ethyl acetate (1/1), and the solution was passed through a column packed with silica gel (100 mL) and then extracted with methylene chloride/ethyl acetate = 1/1 (2 L). The extract was concentrated, and the resulting residue was purified by column chromatography on silica gel (hexane/ethyl acetate = 70/30 to 35/65) to give 4-chloro-5-fluoro-7H-pyrrolo[2, 3-d]pyrimidine (1.30 g) as a powder (yield: 58percent). MS(APCI)m/z; 172/174[M+H]PREPARATION 144-chloro-5-fluoro-1 /-/-pyrrolo[2, 3-c ]pyrimidineA mixture of 6-chloro-7-deazapurine (0.5 g, 3.26 mmol) and SelectfluorThe solution of 4-chloro-7H-pyrrolo[2, 3-d]pyrimi- dine Q-1 (10 g, 65.1 mmol) and Selectfluor (27.7 g, 78.1 mmol) in CH3CN (500 mE) and AcOH (100 mE) was stirred at 70° C. for 16 h. (The reaction was done four times, 10 g of Q-1 in each vessel). The reaction solution turned from colorless to black. TEC (CH2C12/CH3OH=20: 1) showed 20percent of the starting material remained, and then the reaction solution was concentrated to give crude solid. The solid was dissolved in EtOAc (1 E), washed with H20 (300 mEx2). The organic layer was concentrated to give Q-2 (7 g) as brown solid. The combined batch four batches were purified by prep-HPEC (0.225percent formic acid/acetonitrile) to give Q-2 (11.6 g, 26percent) as a white solid. ECMS [M+1] 172; ‘H NMR (400 MHz, DMSO-d5) ö ppm 12.47 (s, 1H), 8.62 (s, 1H), 7.72 (d, 1H)[4-CHLORO-5-BROMO-7H-PYRROLO] [2, 3-d] pyrimidine 2 (0.6 g, 2.60 [MMOL)] was dissolved in 30 mL THF (dry), then [COOLED TO-78°C] before adding 4.10 mL nBuLi (1.6 [M] in hexane) dropwise over a period of 10 minutes. The mixture was stirred for 20 minutes [AT-78°C] before adding 3.38 mmol N- fluorobenzene sulfonimide (NFSI) (1.065 g in 6.5 mL dry THF) dropwise over a period of 15 minutes. The mixture was warmed to room temperature overnight, quenched with 2 mL water, and then evaporated to dryness. The crude preparation obtained was partitioned between ethyl acetate (EtOAc) and a saturated solution of ammonium chloride (40 mL/20 mL) then the aqueous layer was extracted with 20 mL of EtOAc and the combined organic layers were washed with 20 mL water. The organic layer was dried with [MGS04, ] filtered, and the solvent was evaporated. The crude was purified on silica-gel (silica-gel solid deposit in [MEOH)] with 4percent MeOH/CH2CI2 to provide the title compound (0.36 g, [71 percent YIELD)] ; [1H] NMR (DMSO) : [8] 7.70 (s, 1H) ; 8.62 (s, [1H)] ; 12.25 (s, NH)Step 1: Synthesis of To a solution of 5-bromo-4-chloro-7H-pyr- rolo[2, 3-d]pyrimidine (Q-3) (465 mg, 2 mmol) in THF (10 mE, 0.2M) cooled in a dry-ice acetone bath was added l3uEi (2.62 mE, 4.20 mmol, 1.6M) dropwise. The mixture was added to stir at '78° C. for 20 minutes. The reaction mixture became a viscous suspension. A solution ofAccufluor (NFSI) (757 mg, 2.4 mmol) in THF (2 mE, 0.2M) was added drop- wise. Upon complete addition, the reaction mixture became homogenous. The reaction mixture was allowed to slowly warm up to room temperature overnight 16 h. ECMS shows:1 mixture of product to starting material. The reaction mixture was quenched with sat. aq. NH4C1 then diluted with water and EtOAc. The EtOAc was washed with brine, dried with Na2 SO4, filtered and concentrated to an oil. The material was purified by column chromatography on an ISCO column eluting with 0-100percent EtOAc/Heptane to give 75percent pure of Q-2. ECMS [M+1] 172/174; 'HNMR (400 MHz, DMSO-d5) oe ppm 8.62 (s, 1H), 7.71 (d, J=2.2 Hz, 1H)

Molecular Weight:171.56
XLogP3:1.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:170.9999530
Monoisotopic Mass:170.9999530
Topological Polar Surface Area:41.6
Heavy Atom Count:11
Complexity:157
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes