methyl 5-(chloromethyl)furan-2-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred suspension of 4-{5-(cyclopropylcarbonyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidin-4-yl}benzonitrile (Example 22) (150 mg, 0.35 mmol) and potassium carbonate (98 mg, 0.71 mmol) in dimethylformamide (3 ml) is added methyl 5-(chloromethyl)-2-furoate (92 mg, 0.53 mmol). The suspension is stirred at room temperature overnight (16 h), then additional methyl 5-(chloromethyl)-2-furoate (6.1 mg, 0.35 mmol) and potassium carbonate (49 mg, 0.35 mmol) are added, and the suspension is stirred an additional 72 hours. The reaction mixture is diluted with methanol (5 ml) and purified directly by preparative HPLC (RP 18 column; eluent: acetonitrile/water 10:90→90:10). The title compound is isolated as a brownish amorphous solid. the suspension is stirred an additional 72 hours purified directly by preparative HPLC (RP 18 column; eluent: acetonitrile/water 10:90→90:10)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Nitrophenol (1.0 g, 7.19 mmole), methyl 5-(chloromethyl)-2-furoate (1.38 g, 7.90 mmole) and anhydrous K2CO3 (1.19 g, 8.60 mmole) in acetone (30 mL) were refluxed for 8 h. The reaction mixture was cooled and diluted with water. The resultant white solid was filtered, washed with water and air dried overnight to give 1.81 g (90%) of the desired product. 1H NMR (CDCl3): δ 7.86 (dd, 1H, J=2.3 and 8.2 Hz), 7.80 (t, 1H, J=2.3 Hz), 7.45 (t, 1H, J=8.2 Hz), 7.27 (dd, 1H, J=2.3 and 8.2 Hz), 7.17 (d, 1H, J=3.5 Hz), 6.58 (d, 1H, J=3.5 Hz), 5.13 (s, 2H), 3.90 (s, 3H). The reaction mixture was cooled The resultant white solid was filtered washed with water and air dried overnight

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of methyl 5-chloromethyl-2-furoate (5.0g, 28.7mmol) in ethyl acetate (40ml) was hydrogenated over 10% palladium on charcoal (50mg) for 3h. The catalyst was filtered off and washed with ethyl acetate. The combined filtrates were concentrated in vacuo and the residue purified by chromatography on silica gel eluting with 10% ethyl acetate in hexane to yield the title compound as a colourless oil (3.78g, 94%); vmax (CH2Cl2) 1725, 1534, 1522, 1437 and 1311cm-1 ; δH (CDCl3, 90MHz) 2.38 (3H, s), 3.86 (3H, s), 6.12 (1H, br d, J 4Hz) and 7.07 (1H, d, J 4Hz). [Mass spectrum: M+(140)]. The catalyst was filtered off washed with ethyl acetate The combined filtrates were concentrated in vacuo the residue purified by chromatography on silica gel eluting with 10% ethyl acetate in hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydride (60% dispersion in mineral oil, 60 mg, 1.50 mmol) was added to 2,2,2-trifluoroethanol (99 μL, 1.38 mmol) in anhydrous DMF (1 mL) and the mixture was stirred under nitrogen for 20 min. 5-Chloromethylfuran-2-carboxylic acid methyl ester (200 mg, 1.15 mmol) was then added and the mixture was stirred at room temperature for 18 h, then at 60 C for 3 h, then at 100 C for 3 h. Sodium hydride (60% dispersion in mineral oil, 30 mg, 0.75 mmol) was added under nitrogen and the reaction mixture was stirred at room temperature for 18 h. Sodium hydride (60% dispersion in mineral oil, 30 mg, 0.75 mmol) was added and the mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with EtOAc (30 mL) then washed with saturated aq. sodium bicarbonate (4×6 mL), saturated aq. ammonium chloride (2×6 mL) and then brine (6 mL). The aqueous extractions were combined and brought to pH 1 by the addition of 2M HCl and then extracted with DCM (5 mL). The combined organic extractions were washed with water (3×6 mL), then brine (6 mL) and then dried over sodium sulfate and evaporated under vacuum to afford the title compound (123 mg, 48%), which was used without further purification. Method C HPLC-MS: (MH+) requires m/z=225. Found: m/z=252, Rt=1.15 min (97%). the mixture was stirred at room temperature for 18 h at 60 C for 3 h at 100 C for 3 h the reaction mixture was stirred at room temperature for 18 h the mixture was stirred at room temperature for 3 h then washed with saturated aq. sodium bicarbonate (4×6 mL), saturated aq. ammonium chloride (2×6 mL) The aqueous extractions brought to pH 1 by the addition of 2M HCl extracted with DCM (5 mL) The combined organic extractions were washed with water (3×6 mL) brine (6 mL) and then dried over sodium sulfate evaporated under vacuum

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5.00 g of 2'-deoxy-5-fluoro-5'-O-trityluridine in 100 ml of dioxane were added 5.74 g of fine powder of potassium hydroxide and 2.67 g of 5-methoxycarbonylfurfuryl chloride, and the mixture was stirred at temperature of 80° C. for 2.5 hours. The reaction mixture was concentrated and the residue was dissolved in 100 ml of water. The reaction mixture was adjusted to a pH of 4 with one normal hydrochloric acid and then extracted with ethyl acetate. The organic layer was dried and concentrated To the residue was added 100 ml of 80% acetic acid The mixture was left to stand at a temperature of 80° C. for one hour. The solvent was distilled off and the residue was washed with ethyl acetate and methanol, giving 2.53 g (67%) of 3'-O-(5carboxyfurfuryl)-2'-deoxy-5-fluorouridine. The reaction mixture was concentrated the residue was dissolved in 100 ml of water extracted with ethyl acetate The organic layer was dried concentrated To the residue was added 100 ml of 80% acetic acid The mixture was left to stand at a temperature of 80° C. for one hour The solvent was distilled off the residue was washed with ethyl acetate and methanol