1,2-diiodoethane

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:

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:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: t-Buthyllithium (2.7 mL of a 1.7 M solution in pentane, 4.61 mmol) was added to a solution of 1-(N-tert-Butoxycarbonylamino)-6,7-dimethoxynaphthalene (0.50 g, 1.65 mmol) in dry diethyl ether (5.0 mL) and dry DME (2.5 mL) at −40° C. under nitrogen. The resulting mixture was stirred at −20° C. for 5 h and then cooled to −78° C. A solution of 1,2-diiodoethane (1.30 g, 4.61 mmol) in dry DME was added and the resulting solution was allowed to warm to ambient temperature over several hours. Aq. NH4Cl was added, and the mixture was extracted twice with DCM. The combined organic extracts were washed with water, dried, filtered and evaporated to leave a dark glass. The compound was purified by column chromatography to give the pure product 1-(N-tert-Butoxycarbonylamino)-6,7-dimethoxy-4-iodonaphthalene. 1H NMR (200 MHz) (DMSO-d6) δ 1.51 (s, 9H), 3.82 (s, 3H), 3.97 (s, 3H), 7.42 (t, J=8.5 Hz, 1H), 7.48 (s, 1H), 7.57 (d, J=8.5 Hz, 1H), 7.79 (d, J=8.5 Hz, 1H), 9.28 (s, 1H). cooled to −78° C to warm to ambient temperature over several hours the mixture was extracted twice with DCM The combined organic extracts were washed with water dried filtered evaporated to leave a dark glass The compound was purified by column chromatography

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

Procedure: 0.18 ml of 1.6M n-butyl lithium/hexane solution were added to THF solution (10 ml) of 202 mg of N-[1-(2-phenylethyl)-5-bromo-4-ethoxycarbonylpyrazol-3-yl]-N-[(2'-(N-triphenylmethyl-(1H-tetrazol-5-yl))biphenyl-4-yl)methyl]-n-propylamine, while cooling with dry ice-acetone. After stirred for 2 hours, 667 mg of 1,2-diiodoethane were added thereto. After stirred for one hour, the mixture was then stirred at room temperature for further one hour. 10 ml of aqueous ammonium chloride solution were added to the reaction solution, THF was distilled off under reduced pressure, and the resultant was extracted with 50 ml of dichloromethane. After dried over magnesium sulfate, this was subjected to silica gel column chromatography (n-hexane--ethyl acetate=5:1) to obtain 84 mg of the intended compound as a pale red, amorphous solid. After stirred for one hour the mixture was then stirred at room temperature for further one hour was distilled off under reduced pressure the resultant was extracted with 50 ml of dichloromethane After dried over magnesium sulfate

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flask charged with a solution of 6-chloro-1-methyl-1H-benzo[d]imidazole (2 g, 12 mmol) in THF (100 mL) was cooled to −78° C. and 1.8M LDA in THF/hexanes/ethylbenzene (9.34 mL, 16.81 mmol) was added dropwise, and the mixture was stirred at −78° C. for 1 h. A solution of 1,2-diiodoethane (3.72 g, 13.2 mmol) in THF (50 mL) was added dropwise and the mixture was stirred at −78° C. for 1 h. Water (0.3 mL) was added followed by silica gel (20 g) and the mixture was concentrated in vacuo. The residue was purified by silica chromatography eluting with EtOAc in heptane (v/v, 10 to 50%) to give 6-chloro-2-iodo-1-methyl-1H-benzo[d]imidazole. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.76 (s, 3H) 7.19 (dd, J=8.59, 2.02 Hz, 1H) 7.58 (d, J=8.59 Hz, 1H) 7.78 (d, J=2.02 Hz, 1H). the mixture was stirred at −78° C. for 1 h the mixture was concentrated in vacuo The residue was purified by silica chromatography eluting with EtOAc in heptane (v/v, 10 to 50%)

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

Procedure: 0.18 ml of 1.6M n-butyl lithium/hexane solution were added to THF solution (10 ml) of 202 mg of N-[1-(2-phenylethyl)-5-bromo-4-ethoxycarbonylpyrazol-3-yl]-N-[(2'-(N-triphenylmethyl-(1H-tetrazol-5-yl))biphenyl-4-yl)methyl]-n-propylamine, while cooling with dry ice-acetone. After stirred for 2 hours, 667 mg of 1,2-diiodoethane were added thereto. After stirred for one hour, the mixture was then stirred at room temperature for further one hour. 10 ml of aqueous ammonium chloride solution were added to the reaction solution, THF was distilled off under reduced pressure, and the resultant was extracted with 50 ml of dichloromethane. After dried over magnesium sulfate, this was subjected to silica gel column chromatography (n-hexane-ethyl acetate=5:1) to obtain 84 mg of the intended compound as a pale red, amorphous solid. After stirred for one hour the mixture was then stirred at room temperature for further one hour was distilled off under reduced pressure the resultant was extracted with 50 ml of dichloromethane After dried over magnesium sulfate

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

Procedure: 30 ml (48 mmol) of 1.6 M BuLi are added dropwise at −78° C. to a solution of 15.8 g (44 mmol) of 7 in 132 ml of dry THF. After 15 minutes, 16 g (57.2 mmol) of 1,2-diiodoethane are added as solid, and the mixture is allowed to warm to room temperature over the course of 1 hour. Water and methyl tert-butyl ether are subsequently added. The organic phase is washed with water, sat. Na2S2O5 and sat. NaCl, dried over MgSO4 and filtered through SiO2. The solvent is removed under reduced pressure, petroleum ether is added to the oily residue, and the product is recrystallised at −25° C. (yield: 84%, m.p. 76.0° C.). The organic phase is washed with water, sat. Na2S2O5 and sat. NaCl dried over MgSO4 filtered through SiO2 The solvent is removed under reduced pressure, petroleum ether is added to the oily residue the product is recrystallised at −25° C. (yield: 84%, m.p. 76.0° C.)