1,2-二溴-3,4-二甲苯

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

实验步骤: Using the procedure described in Example I, tetraisopropylmethanediphosphonate MDP was converted to the desired ester in 70% yield by reaction with dibromo-o-xylene at 80° C. for 3 h: mp 55°-57° C.; 1H NMR (CDCl3) 7.15 (s, 4H, aromatic), 5.00-4.55 (m, 4H, CH), 3.60 (t, 4H, J=17.6 Hz, CH2), 1.26 (t, 24H, J=6 Hz, CH3); 31P NMR (CDCl3) 24.7 ppm; Cl mass spectrum m/e 447 (MH+). Anal. calcd for C21H36O6P2 : C, 56.49; H, 8.13; P, 13.88. Found: C, 56.71; H, 8.24; P, 14.18.

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

实验步骤: A 100 mL flask is charged with acetonitrile (12 mL) and water (24 mL) and is degassed with argon for about 5 min. Linear peptide (0.01 mmole) and 200 mM ammonium bicarbonate (6 mL) are added followed by at least one peptide (0.012 mmole) such as, but not limited to, 1,3-bis(bromomethyl) benzene, 1,2-bis(bromomethyl)benzene, 1,4-bis(bromomethyl)benzene, 2,6-bis(bromomethyl)pyridine, (E)-1,4-dibromobut-2-ene. The reaction mixture is stirred under argon at room temperature for approximately 2 hours and monitored by LC-MS. After the reaction is complete, the reaction solution is frozen and lyophilized. HPLC purification of the crude lyophilized product followed by lyophilization of fractions containing pure peptide results in the final cyclized product as a white power. is degassed with argon for about 5 min the reaction solution is frozen HPLC purification of the crude lyophilized product containing pure peptide results in the final cyclized product as a white power

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

实验步骤: Using the procedure described in Example I, tetraisopropylmethanediphosphonate MDP was converted to the desired ester in 70% yield by reaction with dibromo-o-xylene at 80° C. for 3 h: mp 55°-57° C.; 1H NMR (CDCl3) 7.15 (s, 4H, aromatic), 5.00-4.55 (m, 4H, CH), 3.60 (t, 4H, J=17.6 Hz, CH2), 1.26 (t, 24H, J=6 Hz, CH3); 31P NMR (CDCl3) 24.7 ppm; Cl mass spectrum m/e 447 (MH+). Anal. calcd for C21H36O6P2 : C, 56.49; H, 8.13; P, 13.88. Found: C, 56.71; H, 8.24; P, 14.18.

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

实验步骤: Using the procedure described in Example I, tetraisopropylmethanediphosphonate MDP was converted to the desired ester in 70% yield by reaction with dibromo-o-xylene at 80° C. for 3 h: mp 55°-57° C.; 1H NMR (CDCl3) 7.15 (s, 4H, aromatic), 5.00-4.55 (m, 4H, CH), 3.60 (t, 4H, J=17.6 Hz, CH2), 1.26 (t, 24H, J=6 Hz, CH3); 31P NMR (CDCl3) 24.7 ppm; Cl mass spectrum m/e 447 (MH+). Anal. calcd for C21H36O6P2 : C, 56.49; H, 8.13; P, 13.88. Found: C, 56.71; H, 8.24; P, 14.18.

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

实验步骤: 70 ml (0.175 moles) of lithium butyl 2.5M in hexane are added, over a period of about 20 minutes, to a solution of 25 g (0.215 moles) of indene in 100 ml of tetrahydrofuran. The mixture is left under stirring for 2 hours, and is then cooled to -10° C. 20 g (0.076 moles) of α,α'-dibromo-o-xylene dissolved in 100 ml of THF are then added, in about 1 hour, so that the temperature of the reaction mixture does not exceed -5° C. At the end, the temperature is left to rise to room temperature, the mixture is hydrolyzed with water and extracted with ethyl ether. The ether extracts, after washing until neutral, and drying on anhydrous sodium sulfate, are evaporated. The residue obtained is purified on a silica gel column using petroleum ether containing 1% of ethyl acetate as eluant. After evaporation of the eluant, 9.5 g of α,α'-bis(1-indenyl)-o-xylene, are obtained, characterized by 1H-NMR analysis, with a yield of 26% with respect to the starting dibromo-o-xylene. The mixture is left are then added, in about 1 hour, so that the temperature of the reaction mixture does not exceed -5° C At the end, the temperature is left to rise to room temperature extracted with ethyl ether after washing until neutral, and drying on anhydrous sodium sulfate are evaporated The residue obtained is purified on a silica gel column After evaporation of the eluant, 9.5 g of α,α'-bis(1-indenyl)-o-xylene are obtained

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

实验步骤: Using the procedure described in Example I, tetraisopropylmethanediphosphonate MDP was converted to the desired ester in 70% yield by reaction with dibromo-o-xylene at 80° C. for 3 h: mp 55°-57° C.; 1H NMR (CDCl3) 7.15 (s, 4H, aromatic), 5.00-4.55 (m, 4H, CH), 3.60 (t, 4H, J=17.6 Hz, CH2), 1.26 (t, 24H, J=6 Hz, CH3); 31P NMR (CDCl3) 24.7 ppm; Cl mass spectrum m/e 447 (MH+). Anal. calcd for C21H36O6P2 : C, 56.49; H, 8.13; P, 13.88. Found: C, 56.71; H, 8.24; P, 14.18.

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

实验步骤: A 100 mL flask is charged with acetonitrile (12 mL) and water (24 mL) and is degassed with argon for about 5 min. Linear peptide (0.01 mmole) and 200 mM ammonium bicarbonate (6 mL) are added followed by at least one peptide (0.012 mmole) such as, but not limited to, 1,3-bis(bromomethyl) benzene, 1,2-bis(bromomethyl)benzene, 1,4-bis(bromomethyl)benzene, 2,6-bis(bromomethyl)pyridine, (E)-1,4-dibromobut-2-ene. The reaction mixture is stirred under argon at room temperature for approximately 2 hours and monitored by LC-MS. After the reaction is complete, the reaction solution is frozen and lyophilized. HPLC purification of the crude lyophilized product followed by lyophilization of fractions containing pure peptide results in the final cyclized product as a white power. is degassed with argon for about 5 min the reaction solution is frozen HPLC purification of the crude lyophilized product containing pure peptide results in the final cyclized product as a white power