2-IODOBENZYLAMINE

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: To a solution of 1-azidomethyl-2-iodo-benzene (6.1 g, 23.4 mmol) in anhydrous THF (100 mL) was added triphenylphosphine (6.8 g, 25.7 mmol) at 0° C. The reaction mixture was slowly warmed up to room temperature and stirred for 16 h. The mixture was diluted with ammonium hydroxide (20 mL) and stirred for 3 h. The mixture was then treated with 2M NaOH (30 mL) and stirred for 1 h. The reaction mixture was acidified to pH 2 by adding 3 M HCl. The mixture was diluted with ether and the layers were separated. The aqueous layer was basified to pH 9 by adding 2 M NaOH and then extracted with CH2Cl2 (×3). The combined organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo to yield an oily residue. The resulting residue was treated with ether and filtered. The filtrate was purified by silica gel column chromatography using 95:5 CH2Cl2:MeOH as an eluent to afford 5.4 g (80%) of 2-iodobenzylamine. stirred for 3 h stirred for 1 h the layers were separated by adding 2 M NaOH extracted with CH2Cl2 (×3) The combined organic phase was dried over anhydrous Na2SO4 concentrated in vacuo to yield an oily residue filtered The filtrate was purified by silica gel column chromatography

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A Schlenk tube was charged with CuI (9.6 mg, 0.050 mmol, 5.0 mol %), 2-azetidinone (86 mg, 1.21 mmol), K3PO4 (430 mg, 2.03 mmol), evacuated, and backfilled with Ar. N,N′-Dimethylethylenediamine (11 μL, 0.103 mmol, 10 mol %), 2-iodobenzylamine (132 μL, 1.00 mmol), and toluene (1 mL) were added under Ar. The Schlenk tube was sealed and the reaction mixture was stirred at 100° C. for 22 h. The resulting suspension was allowed to reach room temperature, poured into a solution of 30% aq ammonia (1 mL) in water (20 mL), and extracted with 3×20 mL CH2Cl2. The combined organic layers were dried (Na2SO4), concentrated, and the residue was purified by flash chromatography on silica gel (2×15 cm, ethyl acetate-methanol 10:1, 15 mL fractions). Fractions 10-20 provided 144 mg of the desired product (82% yield) as a white solid. evacuated The Schlenk tube was sealed to reach room temperature extracted with 3×20 mL CH2Cl2 The combined organic layers were dried (Na2SO4) concentrated the residue was purified by flash chromatography on silica gel (2×15 cm, ethyl acetate-methanol 10:1, 15 mL fractions)

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

Procedure: To a solution of {4-[(2-chloro-5-nitro-pyrimidin-4-ylamino)-methyl]-cyclohexyl}-carbamic acid tert-butyl ester (100 mg, 0.26 mmol) in a mixture of CH2Cl2 (2 mL) and DMF (1 mL) were added 2-iodobenzylamine (192 mg, 0.82 mmol) and DIPEA (135 μL, 1.04 mmoL). The reaction mixture was stirred at room temperature for 16 h and concentrated in vacuo. The resulting residue was diluted with EtOAc and washed with water (×3) and then with brine. The organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by silica gel preparative TLC using 98:2 CH2Cl2:MeOH as an eluent to afford 97 mg (64%) of (4-{[2-(2-iodo-benzylamino)-5-nitro-pyrimidin-4-ylamino]-methyl}-cyclohexyl)-carbamic acid tert-butyl ester. concentrated in vacuo The resulting residue was diluted with EtOAc washed with water (×3) The organic phase was dried over anhydrous Na2SO4 concentrated in vacuo The residue was purified by silica gel preparative TLC

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A Schlenk tube was charged with CuI (9.6 mg, 0.050 mmol, 5.0 mol %), 2-azetidinone (86 mg, 1.21 mmol), K3PO4 (430 mg, 2.03 mmol), evacuated, and backfilled with Ar. N,N′-Dimethylethylenediamine (11 μL, 0.103 mmol, 10 mol %), 2-iodobenzylamine (132 μL, 1.00 mmol), and toluene (1 mL) were added under Ar. The Schlenk tube was sealed and the reaction mixture was stirred at 100° C. for 22 h. The resulting suspension was allowed to reach room temperature, poured into a solution of 30% aq ammonia (1 mL) in water (20 mL), and extracted with 3×20 mL CH2Cl2. The combined organic layers were dried (Na2SO4), concentrated, and the residue was purified by flash chromatography on silica gel (2×15 cm, ethyl acetate-methanol 10:1, 15 mL fractions). Fractions 10–20 provided 144 mg of the desired product (82% yield) as a white solid. evacuated The Schlenk tube was sealed to reach room temperature extracted with 3×20 mL CH2Cl2 The combined organic layers were dried (Na2SO4) concentrated the residue was purified by flash chromatography on silica gel (2×15 cm, ethyl acetate-methanol 10:1, 15 mL fractions)