4-methoxy-4-oxobutanoate

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

Procedure: In a 100 mL round bottom flask, mono-methyl succinate (132 mg, 1 mmol), 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (1.1 mg, 1.1 mmol) and N,N-diisopropyl-ethyl-amine (0.52 mL, 3 mmol) were mixed in THF (5 mL). The reaction solution was stirred at room temperature for ten minutes. S-trans, trans-Farnesyl-L-cysteine (325 mg, 1 mmol) was added to reaction mixture. The reaction solution was stirred at room temperature overnight. Ethyl acetate (50 mL) was added and then washed with saturated ammonium chloride aqueous solution (20 mL×2), DI water (20 mL×2) and brine (20 mL×2) sequentially. The ethyl acetate solution was dried by Na2SO4 and concentrated in vacuo to afford a crude Compound N-17. The crude Compound N-17 was purified by HPLC (110 mg, 25%) to yield Compound N-17. 1H-NMR (500 MHz, MeOH-d4): δ 1.50 (s, 6H), 1.57 (s, 3H), 1.58 (s, 3H), 1.85-1.88 (m, 2H), 1.91-1.96 (m, 4H), 1.99-2.03 (m, 2H), 2.46-2.54 (m, 4H), 2.68 (dd, J=7.5, 13.5 Hz, 1H), 2.90 (dd, J=4.5, 13.5 Hz, 1H), 3.09-3.12 (m, 2H), 3.21 (s, 3H), 4.35 (dd, J=4.5, 7.0 Hz, 1H), 4.98-5.02 (m, 2H), 5.14 (t, J=7.5 Hz, 1H). 13C-NMR (125 MHz, MeOH-d4): δ 16.12, 16.25, 17.79, 25.94, 27.48, 27.79, 30.40, 30.69, 31.73, 35.49, 40.77, 40.89, 52.24, 55.45, 121.82, 125.22, 125.47, 132.08, 136.15, 139.97, 173.57, 174.80, 177.17; ES-MS: mass calcd for Chemical Formula: C23H37NO5S 439.2. Found (M+Na) m/z 462.2. The reaction solution was stirred at room temperature overnight washed with saturated ammonium chloride aqueous solution (20 mL×2), DI water (20 mL×2) and brine (20 mL×2) sequentially The ethyl acetate solution was dried by Na2SO4 concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Butanedioic acid, monomethyl ester (4.0 g, 30.3 mmole) and CDI (5.40 g, 33.3 mmole) were dissolved in anhydrous DMF (15 ml) and stirred at room temperature for 3 hours. (1Z)-N′-hydroxy-2-phenylethanimidamide (5.0 g, 33.3 mmole) was added to above solution and the mixture was stirred at 90° C. for 20 hours. The reaction mixture was concentrated and the residue was diluted with water and EtOAc. The organic layer was washed with water and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (elution with 1:3 ethyl acetate:hexane) to give the desired product as light yellowish oil (5.2 g, 70% yield). LCMS calculated for C13H15N2O3 (M+H): 247.1. found: 247.1. the mixture was stirred at 90° C. for 20 hours The reaction mixture was concentrated the residue was diluted with water and EtOAc The organic layer was washed with water and brine dried over Na2SO4 filtered concentrated The residue was purified by flash chromatography (elution with 1:3 ethyl acetate:hexane)

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

Procedure: Butanedioic acid, monomethyl ester (4.0 g, 30.3 mmole) and CDI (5.40 g, 33.3 mmole) were dissolved in anhydrous DMF (15 ml) and stirred at room temperature for 3 hours. (1Z)-N′-hydroxy-2-phenylethanimidamide (5.0 g, 33.3 mmole) was added to above solution and the mixture was stirred at 90° C. for 20 hours. The reaction mixture was concentrated and the residue was diluted with water and EtOAc. The organic layer was washed with water and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (elution with 1:3 ethyl acetate:hexane) to give the desired product as light yellowish oil (5.2 g, 70% yield). LCMS calculated for C13H15N2O3 (M+H): 247.1. found: 247.1. the mixture was stirred at 90° C. for 20 hours The reaction mixture was concentrated the residue was diluted with water and EtOAc The organic layer was washed with water and brine dried over Na2SO4 filtered concentrated The residue was purified by flash chromatography (elution with 1:3 ethyl acetate:hexane)

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

Procedure: Dicyclohexylcarbodiimide (0.11 moles, 2.26 g), hydroxybenzotriazole (0.011 moles, 1.48 g) and monomethylsuccinate (0.011 moles, 1.45 g) were dissolved in 75 ml of DMF. 2-(3,4-Diaminophenyl)benzonitrile (0.01 moles, 2.0 g) was added. The reaction was stirred at room temperature for 48 hours The solvent was removed in vacuo. The residue was dissolved in ethyl acetate and washed thoroughly with brine. The ethyl acetate solution was dried over sodium sulfate and filtered. The solvent was removed. The residue was purified by HPLC on silica gel eluted with ethyl acetate. The material was dissolved in 400 ml toluene with 5 mg of p-toluenesulfonic acid and refluxed for 8 hours. The solvent was removed. The residue was purified by HPLC on silica gel eluted with ethyl acetate to yield 2.3 g of methyl 3-[5-(2-cyanophenyl)-1H-benzimidazole-2-yl]propionate. (MS). was removed in vacuo The residue was dissolved in ethyl acetate washed thoroughly with brine The ethyl acetate solution was dried over sodium sulfate filtered The solvent was removed The residue was purified by HPLC on silica gel eluted with ethyl acetate The material was dissolved in 400 ml toluene with 5 mg of p-toluenesulfonic acid refluxed for 8 hours The solvent was removed The residue was purified by HPLC on silica gel eluted with ethyl acetate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an ice-cold solution of mono-methyl succinate, (150 g, 1.135 mol) in 900 ml of methylene chloride and 3 ml of N,N-dimethylformamide was added 119 ml (1.26 mol) of oxalyl chloride, while keeping the pot temperature below 5° C. After the addition was complete, the reaction mixture was stirred at 0° C. for 1 hour and then concentrated to vacuo to give a crude yellow liquid, which was used without purification in the Rosenmund reduction. the pot temperature below 5° C After the addition concentrated to vacuo to give a crude yellow liquid, which was used without purification in the Rosenmund reduction

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

Procedure: Mono-methyl succinate (1), wherein alk is methyl, was chlorinated with oxalyl chloride in dimethyl formamide and methylene chloride to afford 3-carbomethoxypropionyl chloride (2). Compound (2) was catalytically hydrogenated over palladium-charcoal catalyst in the presence of 2,6-lutidine to yield 3-carbomethoxypropionaldehyde (3) which was reacted with formylmethylene triphenylphosphorane under Wittig reaction conditions to obtain 5-carbomethoxy-2-pentanal (4). Compound 4 was epoxidized with aqueous hydrogen peroxide in the presence of 1N sodium bicarbonate to afford methyl-4,5-epoxy-6-oxohexanoate (5). Compound (5) was reacted with tridecyltriphenylphosphonium ylid to give methyl-4,5-epoxy-6(Z)-nonadecenoate (6).

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

Procedure: Dicyclohexylcarbodiimide (0.11 moles, 2.26 g), hydroxybenzotriazole (0.011 moles, 1.48 g) and monomethylsuccinate (0.011 moles, 1.45 g) were dissolved in 75 ml of DMF. 2-(3,4-Diaminophenyl)benzonitrile (0.01 moles, 2.0 g) was added. The reaction was stirred at room temperature for 48 hours. The solvent was removed in vacuo. The residue was dissolved in ethyl acetate and washed thoroughly with brine. The ethyl acetate solution was dried over sodium sulfate and filtered. The solvent was removed. The residue was purified by HPLC on silica gel eluted with ethyl acetate. The material was dissolved in 400 ml toluene with 5 mg of p-toluenesulfonic acid and refluxed for 8 hours. The solvent was removed. The residue was purified by HPLC on silica gel eluted with ethyl acetate to yield 2.3 g of methyl 3-[5-(2-cyanophenyl)-1H-benzimidazole-2-yl]propionate. (MS). The solvent was removed in vacuo The residue was dissolved in ethyl acetate washed thoroughly with brine The ethyl acetate solution was dried over sodium sulfate filtered The solvent was removed The residue was purified by HPLC on silica gel eluted with ethyl acetate The material was dissolved in 400 ml toluene with 5 mg of p-toluenesulfonic acid refluxed for 8 hours The solvent was removed The residue was purified by HPLC on silica gel eluted with ethyl acetate

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

Procedure: Dicyclohexylcarbodiimide (0.11 moles, 2.26 g), hydroxybenzotriazole, (0.011 moles, 1.48 g) and monomethylsuccinate (0.011 moles, 1.45 g) were dissolved in 75 ml of DMF. 2-(3,4-Diaminophenyl)benzonitrile (0.01 moles, 2.0 g) was added. The reaction was stirred at room temperature for 48 hours The solvent was removed in vacuo. The residue was dissolved in ethyl acetate and washed thoroughly with brine. The ethyl acetate solution was dried over sodium sulfate and filtered. The solvent was removed. The residue was purified by HPLC on silica gel eluted with ethyl acetate. The material was dissolved in 400 ml toluene with 5 mg of p-toluenesulfonic acid and refluxed for 8 hours. The solvent was removed. The residue was purified by HPLC on silica gel eluted with ethyl acetate to yield 2.3 g of methyl 3-[5-(2-cyanophenyl)-1H-benzimidazole-2-yl]propionate. (MS). was removed in vacuo The residue was dissolved in ethyl acetate washed thoroughly with brine The ethyl acetate solution was dried over sodium sulfate filtered The solvent was removed The residue was purified by HPLC on silica gel eluted with ethyl acetate The material was dissolved in 400 ml toluene with 5 mg of p-toluenesulfonic acid refluxed for 8 hours The solvent was removed The residue was purified by HPLC on silica gel eluted with ethyl acetate