新斯的明EP杂质B

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:70.01; pressure:0.00; stir:

实验步骤: Dilution of the aliquot (2 uL) with DMSO (200 uL).

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of acid 3 (137 mg, 0.5 mmol), 3-dimethylaminophenol (82 mg, 0.6 mmol), DCC (103 mg, 0.5 mmol), and DMAP (12 mg, 0.01 mmol) in THF (2 mL) was stirred for 2 h. The reaction mixture was concentrated in vacuo, the residue dissolved in benzene, washed with H2O and dried (Na2SO4). Column chromatography (10% EtOAc) in benzene gave 13 as a yellow solid (70 mg, 36%), 1H NMR (CDCl3) 8.13, (d, J=7.3 Hz, 1H), 7.90 (d, J=7.4 Hz, 1H), 7.69 (t, J=6.1 Hz, 1H), 7.58 (t, J=7.6 Hz, 1H), 7.22 (dd, J=8.1, 8.1 Hz, 1H), 6.30-6.70 (m, 2H), 5.96 (s, 1H), 4.21 (t, J=5.6 Hz, 2H), 2.69 (t, J=6.5 Hz, 2H), 1.90-2.15 (m, 4H). The reaction mixture was concentrated in vacuo the residue dissolved in benzene washed with H2O dried (Na2SO4)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-(N,N-dimethylamino)phenol (1.0 g)in dichloromethane (20 ml) was added, dropwise, to a solution of phosgene in toluene (1.93M, 30 ml) previously cooled to -5°. The resulting mixture was stirred at a temperature between -5 to 0° to 30', then decanted and concentrated in vacuo to a brown oil (0.63 g). IR: 1784 (C=O), 1616 and 1572 (C=C) cm-1; 1H-NMR: 7.23 (m); 6.65 (dd); 6.53 (dd); 6.50 (m); 2.96 (s). then decanted concentrated in vacuo to a brown oil (0.63 g)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The titled compound was prepared from [5-(4-fluorophenylcarbamoyl)pyrimidin-2-yloxy]acetic acid using 3-dimethylaminophenol (21 mg, 0.15 mmol) as the coupling partner. Concentration (no chromatography) yielded 53 mg (76%) of the titled compound as a pink-purple solid. ESI-MS m/z 411 (MH+), 409 (M−H−). Concentration (no chromatography)

反应条件: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-dimethylaminophenol (6.90 g, 0.05 mole) in 30 ml of acetonitrile was added in 13 minutes to a chilled (15° C.) stirred solution of 0.10 mole sulfamoyl chloride (Preparation 21) in 30 ml of acetonitrile. This was followed by the addition of 14 ml (0.10 mole) of triethylamine. The resultant mixture was stirred at room temperature overnight. The reaction was diluted with ethyl acetate (~60 ml) and then extracted twice with sodium bicarbonate solution. The aqueous layers were back extracted with 1:1 ethyl acetate/acetonitrile once. The organic layers were combined, dried over sodium sulfate, charcoaled, filtered, and evaporated to a black oil weighing 7.57 g. extracted twice with sodium bicarbonate solution The aqueous layers were back extracted with 1:1 ethyl acetate/acetonitrile once dried over sodium sulfate filtered evaporated to a black oil

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 200 mg (0.688 mmol) of 3-(hydroxymethyl)-6-[(tert-butyldimethylsilyloxy)methyl]-1,2-dithiin (U.S. Ser. No. 08/212,096) in 2 mL dry THF was added a solution of 3--N,N-dimethylaminophenol (190 mg, 1.376 mmol) in 2 mL THF, followed by addition of (220 mg, 0.839 mmol) triphenylphosphine. The resulting solution was cooled to 0° C., then 140 μL (155 mg, 0.890 mmol) of diethylazodicarboxylate was added, and the reaction mixture was kept at 0°-5° C. for 3 h until TLC analysis showed the reaction to be complete. For isolation of the products the reaction mixture was chromatographed directly on silica gel column, using ethyl acetate-hexane, 1:3 to yield 3-[tert-butyldimethylsilyloxy)methyl]-6-[[3-(N,N-dimethylamino)-phenyloxy]methyl]-1,2-dithiin (115 mg, 41.1%); 1H-NMR (CDCl3) δ7.3 (bs, 1 H), 7.1 (bs, 1 H), 6.60 (d, J=2.4, 1 H), 6.52 (bd, J=7.27 1 H), 6.42 (d, J=6.0, 1 H), 6.34 (d, J=6.0, 1 H), 4.60 (s, 2 H), 4.26 (s, 2 H), 2.65 (s, 6 H), 0.88 (s, 9 H), 0.07 (s, 6 H). the reaction For isolation of the products the reaction mixture was chromatographed directly on silica gel column

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 200 mg (0.688 mmol) of 3-(hydroxymethyl)-6-[(tert-butyldimethylsilyloxy)methyl]-1,2-dithiin (U.S. Ser. No. 08/212,096) in 2 mL dry THF was added a solution of 3--N,N-dimethylaminophenol (190 mg, 1.376 mmol) in 2 mL THF, followed by addition of (220 mg, 0.839 mmol) triphenylphosphine. The resulting solution was cooled to 0° C., then 140 μL (155 mg, 0.890 mmol) of diethylazodicarboxylate was added, and the reaction mixture was kept at 0°-5° C. for 3 h until TLC analysis showed the reaction to be complete. For isolation of the products the reaction mixture was chromatographed directly on silica gel column, using ethyl acetate-hexane, 1:3 to yield 3-[tert-butyldimethylsilyloxy)methyl]-6-[[3-(N,N-dimethylamino)-phenyloxy]methyl]-1,2-dithiin (115 mg, 41.1%); 1H-NMR (CDCl3) δ7.3 (bs, 1 H), 7.1 (bs, 1 H), 6.60 (d, J=2.4, 1 H), 6.52 (bd, J=7.27 1 H), 6.42 (d, J=6.0, 1 H), 6.34 (d, J=6.0, 1 H), 4.60 (s, 2 H), 4.26 (s, 2 H), 2.65 (s, 6 H), 0.88 (s, 9 H), 0.07 (s, 6 H). the reaction For isolation of the products the reaction mixture was chromatographed directly on silica gel column

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A slurry of 3.0 g of 3-dimethylaminophenol, 6.05 g of milled potassium carbonate and 75 ml of acetone was stirred at room temperature under nitrogen for 30 minutes and then a solution of 7.66 g of α-bromo-3-chloroacetophenone in 75 ml of acetone was added dropwise. The slurry was stirred at room temperature for 72 hours. Filtration and evaporation gave a residue which was purified by high performance liquid chromatography (7:1 hexane-ethyl acetate). The resulting solid was recrystallized from ethyl acetate-hexane to give 3.0 g of 1-(3-chlorophenyl)-2-[3-(dimethylamino)phenoxy]ethanone, m.p. 101°-103° C. Filtration and evaporation gave a residue which was purified by high performance liquid chromatography (7:1 hexane-ethyl acetate) The resulting solid was recrystallized from ethyl acetate-hexane