1-(4-bromophenyl)propan-1-one

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:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolving 5.0 g (23 mmol) of 4′-bromopropiophenon into 50 milliliter of acetic acid, and adding 3.7 g (23 mmol) of bromine while cooling with ice, stirred at the temperature of 10° C. for 3 hours. After the color of bromine disappeared, adding water and an extraction was carried out using dichloro-methane. Washing the organic layer with water, it was dried with the use of sodium sulfate. The solvent was removed by distillation and the resultant crystals were washed with hexane thereby obtaining 4.3 g of 2,4′-dibromopropiophenon (yield: 63%). while cooling with ice an extraction Washing the organic layer with water, it was dried with the use of sodium sulfate The solvent was removed by distillation the resultant crystals were washed with hexane

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolving 5.0 g (23 mmol) of 4′-bromopropiophenon into 50 milliliter of acetic acid, and adding 3.7 g (23 mmol) of bromine while cooling with ice, stirred at the temperature of 10° C. for 3 hours. After the color of bromine disappeared, adding water and an extraction was carried out using dichloro-methane. Washing the organic layer with water, it was dried with the use of sodium sulfate. The solvent was removed by distillation and the resultant crystals were washed with hexane thereby obtaining 4.3 g of 2,4′-dibromopropiophenon (yield: 63%). while cooling with ice an extraction Washing the organic layer with water, it was dried with the use of sodium sulfate The solvent was removed by distillation the resultant crystals were washed with hexane

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

Procedure: A mixture of 1.74 g 4′-bromopropiophenone, 2.0 g ethynyltrimethylsilane, 260 mg bis(triphenylphosphine)palladium(II) dichloride, 260 mg copper(I) iodide and 15 ml diisopropylamine in 40 ml tetrahydrofuran is heated at reflux for 1 h. After cooling the reaction mixture is diluted with water and extracted with ethyl acetate. The combined organic layer is washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue is purified by chromatography on silica gel, using a mixture of heptane/ethyl acetate 9:1 as eluent to obtain 1-(4-trimethylsilanylethynylphenyl)propan-1-one, m.p. 36-37° C. is heated at reflux for 1 h After cooling the reaction mixture extracted with ethyl acetate The combined organic layer is washed with brine dried over sodium sulfate evaporated under reduced pressure The residue is purified by chromatography on silica gel a mixture of heptane/ethyl acetate 9:1 as eluent

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

Procedure: A mixture of 1.74 g 4′-bromopropiophenone, 2.0 g ethynyltrimethylsilane, 260 mg bis(triphenylphosphine)palladium(II) dichloride, 260 mg copper(I) iodide and 15 ml diisopropylamine in 40 ml tetrahydrofuran is heated at reflux for 1 h. After cooling the reaction mixture is diluted with water and extracted with ethyl acetate. The combined organic layer is washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue is purified by chromatography on silica gel, using a mixture of heptane/ethyl acetate 9:1 as eluent to obtain 1-(4-trimethylsilanylethynylphenyl)propan-1-one, m.p. 36-37° C. is heated at reflux for 1 h After cooling the reaction mixture extracted with ethyl acetate The combined organic layer is washed with brine dried over sodium sulfate evaporated under reduced pressure The residue is purified by chromatography on silica gel a mixture of heptane/ethyl acetate 9:1 as eluent

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

Procedure: To a slurry of 16.0 g. of p-bromopropiophenone and 8.0 g. of glyoxylic acid in 90 ml. of water is added (with cooling) a mixture of 20 g. of 50% sodium hydroxide in 280 ml. of ethanol-water (1:1). The mixture is allowed to stand at room temperature for 20 hours and then heated to the boiling point for 30 minutes. The mixture is diluted with 800 ml. of ice and water, stirred several minutes and filtered. The filtrate is acidified with 5 N HCl and filtered to give 12.5 g. of β-(4-bromobenzoyl)crotonic acid as tan crystals, m.p. 137°-144° C. The preceding compound (5.0 g.) is coupled with L-proline with N,N-carbonyldiimidazole in tetrahydrofuran to give 1-[β-(4-bromobenzoyl)crotonyl]-L-proline. A mixture of the preceding compound with thiolacetic acid in acetonitrile gives the product of the example as a glass. (with cooling) a mixture of 20 g heated to the boiling point for 30 minutes The mixture is diluted with 800 ml filtered filtered to give 12.5 g

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

Procedure: To a solution of n-BuLi (2.79 ml, 1.6M solution in hexane, 4.46 mmol) in ether was added solid methyltriphenylphosphonium bromide (1.59 g, 4.46 mmol) in three portions. The mixture was stirred at rt for 4 h, and then a solution of 4-bromopropio-phenone (1.00 g, 4.69 mmol) in ether was added and the mixture was gently refluxed overnight. The mixture was filtered and the filtrate was washed with water and brine, dried (MgSO4), filtered and concentrated in vacuo to give a residue which was purified by flash column chromatography to give 1-bromo-4-(1-methylenepropyl)-benzene (310 mg, 31%) as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ 7.45 (d, J=9.0 Hz, 2H), 7.28 (d, J=9.0 Hz, 2H), 5.26 (m, 1H), 5.07 (m, 1H), 2.48 (q, J=7.5 Hz, 2H), 1.09 (t, J=7.5 Hz, 3H). the mixture was gently refluxed overnight The mixture was filtered the filtrate was washed with water and brine dried (MgSO4) filtered concentrated in vacuo to give a residue which was purified by flash column chromatography

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

Procedure: 4-(1H-Pyrazol-3-yl)-benzonitrile (100 mg, 0.591 mmol), 1-(4-bromophenyl)-propan-1-one (126 mg, 0.591 mmol), Cs2CO3 (770 mg, 2.364 mmol), CuI (4 mg, 0.018 mmol), 8-hydroxyquinoline (3 mg, 0.018 mmol), and DMF/H2O (2 mL; 10:1 solution) were combined in a 10 mL CEM Microwave reaction vessel fitted with magnetic stir bar and subjected to microwave irradiation at 150° C. for 30 min. The contents were then filtered and concentrated to dryness affording the nitrile (158 mg, 0.508 mmol, 86%). Reduction of the nitrile to the corresponding aldehyde was accomplished following the DIBAL procedure described earlier. fitted with magnetic stir bar irradiation at 150° C. for 30 min The contents were then filtered concentrated to dryness

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

Procedure: 4-(1H-Pyrazol-3-yl)-benzonitrile (100 mg, 0.591 mmol), 1-(4-bromophenyl)-propan-1-one (126 mg, 0.591 mmol), Cs2CO3 (770 mg, 2.364 mmol), CuI (4 mg, 0.018 mmol), 8-hydroxyquinoline (3 mg, 0.018 mmol), and DMF/H2O (2 mL; 10:1 solution) were combined in a 10 mL CEM Microwave reaction vessel fitted with magnetic stir bar and subjected to microwave irradiation at 150° C. for 30 min. The contents were then filtered and concentrated to dryness affording the nitrile (158 mg, 0.508 mmol, 86%). Reduction of the nitrile to the corresponding aldehyde was accomplished following the DIBAL procedure described earlier. fitted with magnetic stir bar irradiation at 150° C. for 30 min The contents were then filtered concentrated to dryness

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

Procedure: Prepared by the same method as described in example 1 except that (i) steps A, B and C were omitted; (ii) commercially available 1-(4-bromo-phenyl)-propan-1-one was used in place of 1-(2-fluoro-4-iodo-phenyl)-ethanone in step 106-D and (iii) chlorination of the 5-position of the imidazole ring with N-chlorosuccinimide in step 106-F was omitted. HR-MS: calcd for C30H29BrN4O4 [M+H+] 589.1445. Found 589.1444. Prepared by the same method