2,3,4-trifluorobenzoyl chloride

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: The titled compound was prepared according to the procedure of Method D using the product of Example 83D and 2,3,4-trifluorobenzoyl chloride (Aldrich). 1H NMR (300 MHz, CD3OD) δ 7.40-7.50 (m, J=9.3, 9.3, 7.0, 2.2 Hz, 1H), 8.10-8.20 (m, 1H), 8.39 (dd, J=5.4, 2.4 Hz, 1H), 9.46 (dd, J=5.3, 1.2 Hz, 1H), 9.87 (dd, J=2.2, 1.2 Hz, 1H) ppm; MS (DCI/NH3) m/z=279 (M+H)+.

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

実験手順: 2,3,4-Trifluorobenzoyl chloride (2.32 mL, 18.16 mmol) was added slowly to a stirred mixture of (2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)methylamine (3.44 g, 18.16 mmol) in DCM (200 mL) and 10% aqueous sodium hydroxide solution (200 mL) at 0° C. The reaction was allowed to warm to RT and stirred for a further 24 hours. The phases were separated and the aqueous phase further extracted with DCM (3×100 mL), the combined organics dried (MgSO4), filtered and the solvent removed in vacuo to give a pale yellow oil. The residue was chromatographed on silica, eluting with 0-50% ethyl acetate in isohexane, to give the desired compound as a colourless oil (5.22 g). The phases were separated the aqueous phase further extracted with DCM (3×100 mL) the combined organics dried (MgSO4) filtered the solvent removed in vacuo to give a pale yellow oil The residue was chromatographed on silica eluting with 0-50% ethyl acetate in isohexane

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

実験手順: 2,3,4-Trifluorobenzoylchloride (195 mg, 1 mmol) in DCM (1 mL) was added to a stirred solution of N-benzylaminoethanol (166 mg, 1.1 mmol) in a mixture of DCM (1 mL) and 10% sodium hydroxide solution (1 mL) at 0° C. After the addition of the acid chloride was complete, the mixture was warmed to RT and stirred for approximately 4 hours. The two layers were separated and the aqueous layer was extracted with DCM (3×30 mL). The organic layers were combined, dried (MgSO4), filtered and evaporated to give a colourless oil (190 mg). 1H NMR δ (CDCl3): 3.74 (t, 2H), 3.82 (t, 2H), 4.5 (s, 2H), 4.85 (s, 1H), 7.06 (td, 1H), 7.15 (m, 1H), 7.28-7.37 (m, 1H). m/z 310 (M+H)+ The two layers were separated the aqueous layer was extracted with DCM (3×30 mL) dried (MgSO4) filtered evaporated

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

実験手順: 2,3,4-Trifluorobenzoylchloride (195 mg, 1 mmol) in DCM (1 mL) was added to a stirred solution of N-benzylaminoethanol (166 mg, 1.1 mmol) in a mixture of DCM (1 mL) and 10% sodium hydroxide solution (1 mL) at 0° C. After the addition of the acid chloride was complete, the mixture was warmed to RT and stirred for approximately 4 hours. The two layers were separated and the aqueous layer was extracted with DCM (3×30 mL). The organic layers were combined, dried (MgSO4), filtered and evaporated to give a colourless oil (190 mg). 1H NMR δ (CDCl3): 3.74 (t, 2H), 3.82 (t, 2H), 4.5 (s, 2H), 4.85 (s, 1H), 7.06 (td, 1H), 7.15 (m, 1H), 7.28-7.37 (m, 1H). m/z 310 (M+H)+ The two layers were separated the aqueous layer was extracted with DCM (3×30 mL) dried (MgSO4) filtered evaporated

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

実験手順: DIPEA (0.68 mL, 3.9 mmol) was added to a solution of 2,3,4-trifluorobenzoyl chloride (500 mg, 2.6 mmol) in DCM (5 mL) followed by the addition of N-methylethanolamine (0.31 mL, 3.9 mmol). The mixture was stirred for 20 hours. The solution was diluted with methanol (10 mL) and passed through an ISOLUTE® SCX-2 SPE column. The solution was evaporated. The residue was dissolved in DMF and sodium hydride (60% dispersion in mineral oil, 0.11 g, 2.7 mmol) was added portionwise over 5 minutes. The resulting mixture was stirred for 20 hours. Water (100 mL) was added dropwise and the mixture was extracted with ether (3×200 mL). Combined ethereal extracts were dried (MgSO4) and evaporated. The residue was purified by column chromatography (eluting with 1:1 ethyl acetate:isohexane to neat ethyl acetate) to afford the title compound (117 mg, 20%) as a colourless solid. The solution was evaporated The residue was dissolved in DMF The resulting mixture was stirred for 20 hours the mixture was extracted with ether (3×200 mL) were dried (MgSO4) evaporated The residue was purified by column chromatography (eluting with 1:1 ethyl acetate:isohexane to neat ethyl acetate)

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

実験手順: DIPEA (0.68 mL, 3.9 mmol) was added to a solution of 2,3,4-trifluorobenzoyl chloride (500 mg, 2.6 mmol) in DCM (5 mL) followed by the addition of N-methylethanolamine (0.31 mL, 3.9 mmol). The mixture was stirred for 20 hours. The solution was diluted with methanol (10 mL) and passed through an ISOLUTE® SCX-2 SPE column. The solution was evaporated. The residue was dissolved in DMF and sodium hydride (60% dispersion in mineral oil, 0.11 g, 2.7 mmol) was added portionwise over 5 minutes. The resulting mixture was stirred for 20 hours. Water (100 mL) was added dropwise and the mixture was extracted with ether (3×200 mL). Combined ethereal extracts were dried (MgSO4) and evaporated. The residue was purified by column chromatography (eluting with 1:1 ethyl acetate:isohexane to neat ethyl acetate) to afford the title compound (117 mg, 20%) as a colourless solid. The solution was evaporated The residue was dissolved in DMF The resulting mixture was stirred for 20 hours the mixture was extracted with ether (3×200 mL) were dried (MgSO4) evaporated The residue was purified by column chromatography (eluting with 1:1 ethyl acetate:isohexane to neat ethyl acetate)

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

実験手順: The titled compound was prepared according to the procedure of Method D using the product of Example 83D and 2,3,4-trifluorobenzoyl chloride (Aldrich). 1H NMR (300 MHz, CD3OD) δ 7.40-7.50 (m, J=9.3, 9.3, 7.0, 2.2 Hz, 1 H), 8.10-8.20 (m, 1 H), 8.39 (dd, J=5.4, 2.4 Hz, 1 H), 9.46 (dd, J=5.3, 1.2 Hz, 1 H), 9.87 (dd, J=2.2, 1.2 Hz, 1 H) ppm; MS (DCI/NH3) m/z=279 (M+H)+.

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir: