(3-iodophenyl)methanamine

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:0.00; pressure:0.00; stir:

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

Procedure: A 100 mL, three-necked, round-bottomed flask was equipped with a magnetic stirrer, a heating mantle, a standard condenser with a N2 inlet, and two glass stoppers. A mixture containing 3-iodobenzylamine (1.19 g, 5.10 mmol), paraformaldehyde (1.22 g, 40.8 mmol), and CH3OH (30 mL) was made acidic with glacial acetic acid (0.46 g, 7.65 mmol). In one portion, 4-thianone (44, 0.59 g, 5.10 mmol) was added and the resulting mixture was heated under N2 at reflux for 21 h. Evaporation of the solvent gave a reddish oil, which was dissolved in H2O (40 mL). Basification (pH~13) of the solution by the dropwise addition of 10% NaOH resulted in the formation of a milky suspension which was extracted with ether (5×40 mL). Combined extracts were dried (Na2SO4, overnight), filtered, and concentrated to a yellow oil. Digestion of the oil occurred in Skelly B (125 mL, bp 60°-68° C.) for 30 min, and the supernatant was decanted. Further digestion of the residual material was effected in pentane (2×125 mL) for 30 min. Combined supernatant extracts were concentrated (rotary evaporator the vacuum pump, overnight, RT/0.2 mm Hg) to give 0.84 g (57.5%) of a slightly crude viscous oil (25) which was used without further purification in the next step. IR (film) cm-1 3055 (Ar C--H), 2930, 2825 (C--H), 1735 (C=O), 885, 790, 695 (C--H out of plane, meta); 1H NMR (DCCl3) δ2.72-3.18 [m, 10 H, ring protons and H(1,5)], 3.51 (s, 2 H, ArCH2), 7.07-7.71 (m, 4 H, Ar--H); 13C NMR (DCCl3) ppm 35.05 [C(2,4)], 46.95 [C(1,5)], 58.20 [C(6,8)], 60.69 (ArCH2), 94.43, 127.98, 130.23, 136.44, 137.64, 140.63 (Ar--C), 213.00 (C=O). A 100 mL, three-necked, round-bottomed flask was equipped with a magnetic stirrer the resulting mixture was heated under N2 at reflux for 21 h Evaporation of the solvent gave a reddish oil, which resulted in the formation of a milky suspension which was extracted with ether (5×40 mL) Combined extracts were dried (Na2SO4, overnight) filtered concentrated to a yellow oil the supernatant was decanted Further digestion of the residual material was effected in pentane (2×125 mL) for 30 min were concentrated ( rotary evaporator the vacuum pump, overnight, RT/0.2 mm Hg)

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

Procedure: 2-Chloro-6-[(3-iodobenzyl)amino]-9-cyclopentenylpurine is prepared from 2,6-dichloro-9-cyclopentenylpurine, 3-iodobenzylamine, and triethylamine essentially as described above in Example 1, Scheme A, step b.

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 %), δ-valerolactam (120 mg, 1.21 mmol), K3PO4 (430 mg, 2.03 mmol), briefly evacuated and backfilled with argon. N,N′-Dimethylethylenediamine (11 μL, 0.10 mmol, 10 mol %), 3-iodobenzylamine (134 μL, 1.01 mmol), and toluene (1.0 mL) were added under argon. The Schlenk tube was sealed with a Teflon valve and the reaction mixture was stirred at 100° C. for 18 h. The resulting pale yellow suspension was allowed to reach room temperature, and then 30% aq ammonia (1 mL) and water (10 mL) were added. The biphasic mixture was extracted with CH2Cl2 (3×15 mL). The combined organic phases were dried (Na2SO4), concentrated, and the residue was purified by flash chromatography on silica gel (2×15 cm; CH2Cl2(saturated with 30% aq ammonia)-CH2Cl2-MeOH 10:10:1; 15 mL fractions). Fractions 14-19 provided 199 mg (96% yield) of the product as a pale yellow oil. briefly evacuated The Schlenk tube was sealed with a Teflon valve to reach room temperature The biphasic mixture was extracted with CH2Cl2 (3×15 mL) The combined organic phases were dried (Na2SO4) concentrated the residue was purified by flash chromatography on silica gel (2×15 cm; CH2Cl2(saturated with 30% aq ammonia)-CH2Cl2-MeOH 10:10:1; 15 mL fractions)

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 %), δ-valerolactam (120 mg, 1.21 mmol), K3PO4 (430 mg, 2.03 mmol), briefly evacuated and backfilled with argon. N,N′-Dimethylethylenediamine (11 μL, 0.10 mmol, 10 mol %), 3-iodobenzylamine (134 μL, 1.01 mmol), and toluene (1.0 mL) were added under argon. The Schlenk tube was sealed with a Teflon valve and the reaction mixture was stirred at 100° C. for 18 h. The resulting pale yellow suspension was allowed to reach room temperature, and then 30% aq ammonia (1 mL) and water (10 mL) were added. The biphasic mixture was extracted with CH2Cl2 (3×15 mL). The combined organic phases were dried (Na2SO4), concentrated, and the residue was purified by flash chromatography on silica gel (2×15 cm; CH2Cl2(saturated with 30% aq ammonia)-CH2Cl2-MeOH 10:10:1; 15 mL fractions). Fractions 14-19 provided 199 mg (96% yield) of the product as a pale yellow oil. briefly evacuated The Schlenk tube was sealed with a Teflon valve to reach room temperature The biphasic mixture was extracted with CH2Cl2 (3×15 mL) The combined organic phases were dried (Na2SO4) concentrated the residue was purified by flash chromatography on silica gel (2×15 cm; CH2Cl2(saturated with 30% aq ammonia)-CH2Cl2-MeOH 10:10:1; 15 mL fractions)