布南色林杂质33

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:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 4-fluorobenzoylacetonitrile (2.84 g), 2,5-dihydroxy-1,4-dithian (1.31 g), triethylamine (2.2 ml) and ethanol (15 ml) was stirred for 40 minutes at 50° C. The reaction mixture was cooled to give 2-amino-3-(4-fluorobenzoyl)thiophene as yellow crystals (2.22 g). The reaction mixture was cooled

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-fluorobenzoylacetonitrile (50 g, 306 mmol, 1 eq.) in EtOH (600 mL) was added pyridine (24.7 mL, 306 mmol, 1 eq.). The resulting mixture was stirred at 70° C. for 15 min then cooled to r.t. A previously stirred suspension of thiourea (46.7 g, 613 mmol, 2 eq.) and iodine (77.8 g, 306 mmol, 1 eq.) in EtOH (300 mL) was then slowly added. After 1 h at r.t. a cold 1 M Na2S2O3 solution (360 mL) was added under stirring. The resulting precipitate was filtered, washed with water, and finally dried under vacuo to afford 2-Amino-4-(4-fluoro-phenyl)-thiazole-5-carbonitrile. then cooled to r.t was then slowly added under stirring The resulting precipitate was filtered washed with water finally dried under vacuo

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

实验步骤: Trithiocarbonate (0.644 g, 2.15 mmol) from step (i) was added to a stirred suspension of sodium hydride (0.165 g, 0.412 mmol) in benzene (2.0 mL). Then, 3-(4-fluorophenyl)-3-oxopropanenitrile (0.320 g, 1.96 mmol) was added as a solution in benzene (2.0 mL). The reaction mixture was stirred for 5 min then DMF (2.0 mL) was added slowly. After addition was complete the reaction mixture was heated to reflux for 30 min and then allowed to cool to ambient temperature before being partitioned between H2O and Et2O. The aqueous layer was separated and washed with two additional portions of Et2O, then acidified with aqueous 2 N HCl. The acidic aqueous layer was then extracted with two portions of EtOAc, which were combined, washed with brine, dried over Na2SO4, and concentrated. The residue was purified by flash chromatography, eluting with a gradient of 25-100% EtOAc/hexanes to afford the product as a yellow solid (0.20 g, 0.60 mmol, 31% yield). MS (M-H)− 332. After addition was heated to reflux for 30 min before being partitioned between H2O and Et2O The aqueous layer was separated washed with two additional portions of Et2O The acidic aqueous layer was then extracted with two portions of EtOAc, which washed with brine dried over Na2SO4 concentrated The residue was purified by flash chromatography eluting with a gradient of 25-100% EtOAc/hexanes

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following a procedure described in J. Med. Chem. 2002, 45, 382-389; 0.44 g (2.7 mmol) 3-(4-fluoro-phenyl)-3-oxo-propionitrile (the preparation of which is described in example 17), 0.33 g (2.15 mmol) [1,4]dithiane-2,5-diol, 0.16 ml (2.15 mmol) diethyl-amine and 5 ml ethanol were charged in a sealed tube. The reaction mixture was heated at 50° C. for 6 h. The tube was then placed in a fridge (about 4° C.) for the night, and the product was collected by filtration and dried under vacuum to afford 0.41 g (69%) (2-amino-thiophen-3-yl)-(4-fluoro-phenyl)-methanone as a light brown crystals. were charged in a sealed tube was then placed in a fridge (about 4° C.) for the night the product was collected by filtration dried under vacuum

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

实验步骤: To a stirred suspension of 2.5 g (11.5 mmol) 2-bromo-1-(4-fluoro-phenyl)-ethanone (the preparation of which is described in example . . . ) in 40 ml ethanol was added a solution of 0.90 g (23 mmol) potassium cyanide in 9 ml water. The mixture was then stirred at RT for 2 h, then acidified to ph=5-6 with aqueous HCl 1M and then extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Flash chromatography (heptane/ethyl acetate 6:1) afforded 0.11 g (6%) 3-(4-fluoro-phenyl)-3-oxo-propionitrile as a yellow solid. the preparation of which extracted with ethyl acetate The combined organic phases were dried over sodium sulfate concentrated in vacuo

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

实验步骤: A solution of 16.3 g. of p-fluorobenzoylacetonitrile and 18.3 ml. of triethyl orthoacetate in 35 ml. of acetic anhydride is heated on a steam bath for 2.5 hours. The solvents are removed in vacuo and the residue is distilled at 165°-167° C./300μ. Upon cooling, this distillate solidifies and is recrystallized from methylene chloride/hexane to give the desired 2-(p-fluorobenzoyl)-3-ethoxycrotononitrile, m.p. 77°/89° C. The solvents are removed in vacuo the residue is distilled at 165°-167° C./300μ Upon cooling this distillate solidifies and is recrystallized from methylene chloride/hexane

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

实验步骤: A solution containing 55.8 g. (0.34 mole) of p-fluorobenzoylacetonitrile, 41 g. (0.34 mole) of trimethyl orthoacetate, and 90 g. (0.88 mole) of acetic anhydride is heated to reflux for 5 hours. The excess solvent and volatile by-products are then removed by vacuum distillation and the residue is recrystallized from diethyl ether. Alternatively, the distillation residue may be distilled over on a Kugelrohr apparatus at 160° C./0.25 mm. to provide a viscous oil which may be crystallized from diethyl ether to provide the pure title compound. A solution containing 55.8 g to reflux for 5 hours The excess solvent and volatile by-products are then removed by vacuum distillation the residue is recrystallized from diethyl ether Alternatively, the distillation residue may be distilled over on a Kugelrohr apparatus at 160° C./0.25 mm to provide a viscous oil which may be crystallized from diethyl ether

反应条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1.6 g. of p-fluorobenzoylacetonitrile [Pihl et al., Reakts. Sposobnost Org. Soedin. Tartu. Gos. Univ., 5 (1), 27, (1968)] in 30 ml. of chloroform, cooled to -10° C., is added 1.4 g. of N,N-dimethylacetamide dimethylacetal. The reaction mixture is stirred at -10° C. for 2 hours and then evaporated in vacuo to an oil. This oil is dissolved in 150 ml. of benzene and filtered through Magnesol®. The filtrate is evaporated to 50 ml. and petroleum ether is added to effect crystallization. The product is collected by filtration and then recrystallized from benzene-petroleum ether with charcoal treatment giving the desired product. is added 1.4 g evaporated in vacuo to an oil This oil is dissolved in 150 ml of benzene and filtered through Magnesol® The filtrate is evaporated to 50 ml and petroleum ether is added to effect crystallization The product is collected by filtration recrystallized from benzene-petroleum ether with charcoal treatment