O-cyclopentylhydroxylamine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (4-Methylsulfonyl-phenyl)-oxo-acetic acid ethyl ester (218 mg, 0.85 mmol) was stirred in ethanol (1.7 mL) and warmed in a 70° C. oil bath. O-Cyclopentyl-hydroxylamine (prepared as in Example 1, 146 mg, 1.06 mmol) was added. After 2 h, the reaction mixture was allowed to cool and concentrated in vacuo. Purification by flash column chromatography (Merck silica gel 60, 40-63 □m; 30% ethyl acetate/hexanes to 75% ethyl acetate/hexanes) afforded (E)-cyclopentyloxyimino-(4-methanesulfonyl-phenyl)-acetic acid ethyl ester (60 mg, 21%) as a clear, colorless film containing an unidentified impurity: LC-MS (ESI) m/e calcd for C16H21NO5S [M+] 339.11, found 340 [M+H+]. to cool concentrated in vacuo Purification by flash column chromatography (Merck silica gel 60, 40-63 □m; 30% ethyl acetate/hexanes to 75% ethyl acetate/hexanes)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (3,4-Dichloro-phenyl)-oxo-acetic acid ethyl ester (1.08 g, 4.37 mmol) was stirred in ethanol (9.7 mL) and warmed in a 70° C. oil bath. O-Cyclopentyl-hydroxylamine (prepared as in Example 1, 722 mg, 5.25 mmol) was added. After 2 h, the reaction mixture was allowed to cool and concentrated in vacuo. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 33% methylene chloride/hexanes) afforded (E)-cyclopentyloxyimino-(3,4-dichloro-phenyl)-acetic acid ethyl ester (371 mg, 26%) as a clear, colorless oil: H1-NMR (400 MHz, CDCl3) δ=1.37 (3H, t, J=7.1 Hz), 1.63 (4H, m), 1.85 (4H, m), 4.36 (2H, q, J=7.1 Hz), 4.94 (1H, m), 7.26 (1H, dd, J=8.3 Hz, J=1.9 Hz), 7.46 (1H, d, J=8.3 Hz), 7.54 (1H, d, J=1.9 Hz). to cool concentrated in vacuo Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 33% methylene chloride/hexanes)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (3,4-Dichloro-phenyl)-oxo-acetic acid ethyl ester (1.08 g, 4.37 mmol) was stirred in ethanol (9.7 mL) and warmed in a 70° C. oil bath. O-Cyclopentyl-hydroxylamine (prepared as in Example 1, 722 mg, 5.25 mmol) was added. After 2 h, the reaction mixture was allowed to cool and concentrated in vacuo. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 33% methylene chloride/hexanes) afforded (E)-cyclopentyloxyimino-(3,4-dichloro-phenyl)-acetic acid ethyl ester (371 mg, 26%) as a clear, colorless oil: H1-NMR (400 MHz, CDCl3) δ=1.37 (3H, t, J=7.1 Hz), 1.63 (4H, m), 1.85 (4H, m), 4.36 (2H, q, J=7.1 Hz), 4.94 (1H, m), 7.26 (1H, dd, J=8.3 Hz, J=1.9 Hz), 7.46 (1H, d, J=8.3 Hz), 7.54 (1H, d, J=1.9 Hz). to cool concentrated in vacuo Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 33% methylene chloride/hexanes)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (3-Chloro-4-methanesulfonyl-phenyl)-oxo-acetic acid methyl ester (1.75 g, 6.32 mmol) was stirred in methanol (14 mL) and warmed in a 70° C. oil bath. O-Cyclopentyl-hydroxylamine (1.09 g, 7.92 mmol) was added. After 2 h, the reaction mixture was allowed to cool and concentrated in vacuo. Purification by flash column chromatography (Merck silica gel 60, 40-63 □m; 20% ethyl acetate/hexanes) gave (E)-(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxyimino-acetic acid methyl ester (1.01 g, 44%) eluting second as a clear, colorless oil which solidified over time: H1-NMR (400 MHz, CDCl3) δ=1.62 (4H, m), 1.85 (4H, m), 3.31 (3H, s), 3.91 (3H, s), 4.96 (1H, m), 7.48 (1H, dd, J=8.2 Hz, J=1.3 Hz), 7.59 (1H, d, J=1.2 Hz), 8.17 (1H, d, J=8.2 Hz). to cool concentrated in vacuo Purification by flash column chromatography (Merck silica gel 60, 40-63 □m; 20% ethyl acetate/hexanes)

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: O-cyclopentylhydroxylamine (0.3 mL) was added to a solution of 6-[3-chloro-4-(methylsulfonyl)benzoyl]-3-methylpyridin-2(1H)-one (220 mg) in n-butanol (2 mL) at room temperature, and the mixture was stirred under microwave irradiation at 200° C. for two hours. O-cyclopentylhydroxylamine (0.3 mL) was further added at room temperature, and the mixture was stirred under microwave irradiation at 200° C. for three hours. Water was added to the reaction solution, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1→1:1) and further purified by silica gel column chromatography (chloroform:ethyl acetate=50:1→25:1). The resulting less polar product was powdered with an ethyl acetate/hexane solution, and filtration operation gave (E)-6-{[3-chloro-4-(methylsulfonyl)phenyl](cyclopentyloxyimino)methyl}-3-methylpyridin-2(1H)-one as a white solid (95 mg, 34%). The more polar product was powdered with an ethyl acetate/hexane solution, and filtration operation gave (Z)-6-{[3-chloro-4-(methylsulfonyl)phenyl](cyclopentyloxyimino)methyl}-3-methylpyridin-2(1H)-one as a white solid (36 mg, 13%). the mixture was stirred under microwave irradiation at 200° C. for three hours followed by extraction with chloroform The organic layer was dried over anhydrous magnesium sulfate filtered The solvent was then evaporated under reduced pressure The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1→1:1) further purified by silica gel column chromatography (chloroform:ethyl acetate=50:1→25:1) The resulting less polar product was powdered with an ethyl acetate/hexane solution, and filtration operation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared according to method A as described in example 6 by reacting O-cyclopentylhydroxylamine (prepared by the overall procedure described in example 5) (0.78 g, 5.67 mmol) with 9-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (3.0 g, 4.74 mmol), followed by debenzoylation of the purified product using methanolic ammonia to provide the title 2-chloro-N-cyclopentyloxyadenosine (0.11 g) (after column chromatography) as a solid, mp 116°-119° C., 1H NMR (DMSO-d6)γ 1.50-1.80 (8H, m, --CH2CH2CH2CH2 --), 3.52-3.58 (1H, m, H-5'a), 3.63-3.70 (1H, m, H-5'b), 3.94 (1H, q, H-4'), 4.13 (1H, q, H-3'), 4.51 (1H, q, H-2'), 4.57 (1H, br m,--OCH--), 5.06 (1H, t, 5'-- OH), 5.22, 5.50 (2H, 2d, 2'-and 3'--OH), 5.86 (1H, d, H-1'), 8.46 (1H, s, H-8), 11.40 (1H, s, N-H). The title compound was prepared prepared by the overall procedure

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (4-Methylsulfonyl-phenyl)-oxo-acetic acid ethyl ester (218 mg, 0.85 mmol) was stirred in ethanol (1.7 mL) and warmed in a 70° C. oil bath. O-Cyclopentyl-hydroxylamine (prepared as in Example 1, 146 mg, 1.06 mmol) was added. After 2 h, the reaction mixture was allowed to cool and concentrated in vacuo. Purification by flash column chromatography (Merck silica gel 60, 40-63 □m; 30% ethyl acetate/hexanes to 75% ethyl acetate/hexanes) afforded (E)-cyclopentyloxyimino-(4-methanesulfonyl-phenyl)-acetic acid ethyl ester (60 mg, 21%) as a clear, colorless film containing an unidentified impurity: LC-MS (ESI) m/e calcd for C16H21NO5S [M+] 339.11, found 340 [M+H+]. to cool concentrated in vacuo Purification by flash column chromatography (Merck silica gel 60, 40-63 □m; 30% ethyl acetate/hexanes to 75% ethyl acetate/hexanes)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (3,4-Dichloro-phenyl)-oxo-acetic acid ethyl ester (1.08 g, 4.37 mmol) was stirred in ethanol (9.7 mL) and warmed in a 70° C. oil bath. O-Cyclopentyl-hydroxylamine (prepared as in Example 1, 722 mg, 5.25 mmol) was added. After 2 h, the reaction mixture was allowed to cool and concentrated in vacuo. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 33% methylene chloride/hexanes) afforded (E)-cyclopentyloxyimino-(3,4-dichloro-phenyl)-acetic acid ethyl ester (371 mg, 26%) as a clear, colorless oil: H1-NMR (400 MHz, CDCl3) δ=1.37 (3H, t, J=7.1 Hz), 1.63 (4H, m), 1.85 (4H, m), 4.36 (2H, q, J=7.1 Hz), 4.94 (1H, m), 7.26 (1H, dd, J=8.3 Hz, J=1.9 Hz), 7.46 (1H, d, J=8.3 Hz), 7.54 (1H, d, J=1.9 Hz). to cool concentrated in vacuo Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 33% methylene chloride/hexanes)