3-iodobenzamide

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

Procedure: A mixture of 3-iodobenzamide (4.28 g, 17.3 mmol), water (25.00 g, 1387.7 mmol), triethylamine (8.00 g, 79.1 mmol), palladium(II) acetate (0.28 g, 1.2 mmol), and bis(diphenylphosphino)propane (0.52 g, 1.3 mmol) in acetonitrile (50 mL) was pressurized to 40 psi with carbon monoxide and the pressure was released. After six such cycles, the bottle was pressurized again and the contents were stirred at 85° C. for 3 h. The reaction mixture was cooled to room temperature and depressurized. The solvent was evaporated and ethyl acetate (200 mL) was added. The solution was filtered and then extracted with water (2×200 mL). The combined aqueous layers were acidified with 12 M HCl to pH 0. The solid was filtered off and air-dried to give 3-carboxybenzamide (1.93 g, 87%) as a yellow solid The reaction mixture was cooled to room temperature The solvent was evaporated ethyl acetate (200 mL) was added The solution was filtered extracted with water (2×200 mL) The solid was filtered off air-dried

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

Procedure: 3-Iodo-benzamide compound 32 (3.0 g, 12.1 mmol), N-methoxy-N-methylacrylamide (Molander, G. G.; Stengel, P. J. Tetrahedron 1997, 53, 26, 8887-8912.) (1.8 g, 15 mmol), palladium (II) acetate (40 mg, 0.18 mmol), and triethylamine (2.1 mL, 15 mmol) were stirred in acetonitrile (12 mL) under argon in a sealed tube at 100° C. for 2.5 h. The reaction was allowed to cool, and solvent was removed. The residue was dissolved in CH2Cl2, washed with 0.1 N HCl and then with brine, dried (MgSO4), and concentrated. Recrystallization twice from methanol gave 1.64 g (58%) of 3-[2-(methoxy-methylcarbamoyl)-vinyl]benzamide 43 as a white solid. 1H NMR (CDCl3) δ 8.06 (1 H, s), 7.78 (1 H, d, J=7.8 Hz), 7.73 (1 H, d, J=16.2 Hz), 7.69 (1 H, d, J=7.8 Hz), 7.46 (1 H, t, J 7.8 Hz), 7.10 (1 H, d, J=16.2 Hz), 6.33 (1 H, br s), 5.97 (1 H, br s), 3.77 (3 H, s), 3.31 (3 H, s); IR (KBr) 3385, 3173, 1680, 1649, 1613, 1582, 1476, 1433, 1397, 1182, 1105 cm−1. Anal. (C12H14N2O3.0.33 H2O) C, H, N. to cool solvent was removed The residue was dissolved in CH2Cl2 washed with 0.1 N HCl with brine, dried (MgSO4) concentrated Recrystallization twice from methanol

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

Procedure: 3-Iodo-benzamide was prepared using a modification of the procedure by Remsen. (Remsen; Reid Am. Chem. J. 1899, 21, 289.) 3-Iodo-benzoic acid (28.68 g, 116 mmol) was stirred in CH2Cl2 (200 mL) at 23° C. under argon. Oxalyl chloride (30.2 mL, 349 mmol) was added slowly, and slow gas evolution was observed. DMF (0.1 mL) was then added, accelerated gas evolution considerably, and the reaction was stirred for. 2 h. Solvent was removed, and the brown oily residue was dissolved in THF (50 mL) and added to a solution of 18% aqueous NH4OH (260 mL) at 0° C. After stirring the mixture for 15 min, the liquid was decanted off, and the remaining sludge was acidified with 1 N HCl. The white solid was collected by filtration, washed with water, and dried under vacuum to give 25.68 g (90%) of 3-iodo-benzamide compound 32. 1H NMR (DMSO-d6) δ 8.21 (1 H, t, J=1.5 Hz), 8.05 (1 H, s), 7.87 (2 H, dd, J=8.1, 1.5 Hz), 7.47 (1 H, s), 7.25 (1 H, t, J=7.8 Hz); IR (KBr) 3343, 3164, 1661, 1628, 1561, 1424, 1389, 1125. Anal. (C7H6INO) C, H, N. 3-Iodo-benzamide was prepared 2 h Solvent was removed the brown oily residue was dissolved in THF (50 mL) added to a solution of 18% aqueous NH4OH (260 mL) at 0° C After stirring the mixture for 15 min the liquid was decanted off The white solid was collected by filtration washed with water dried under vacuum

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

Procedure: 3-Iodo-benzamide was prepared using a modification of the procedure by Remsen. (Remsen; Reid Am. Chem. J. 1899, 21, 289.) 3-Iodo-benzoic acid (28.68 g, 116 mmol) was stirred in CH2Cl2 (200 mL) at 23° C. under argon. Oxalyl chloride (30.2 mL, 349 mmol) was added slowly, and slow gas evolution was observed. DMF (0.1 mL) was then added, accelerated gas evolution considerably, and the reaction was stirred for. 2 h. Solvent was removed, and the brown oily residue was dissolved in THF (50 mL) and added to a solution of 18% aqueous NH4OH (260 mL) at 0° C. After stirring the mixture for 15 min, the liquid was decanted off, and the remaining sludge was acidified with 1 N HCl. The white solid was collected by filtration, washed with water, and dried under vacuum to give 25.68 g (90%) of 3-iodo-benzamide compound 32. 1H NMR (DMSO-d6) δ 8.21 (1 H, t, J=1.5 Hz), 8.05 (1 H, s), 7.87 (2 H, dd, J=8.1, 1.5 Hz), 7.47 (1 H, s), 7.25 (1 H, t, J=7.8 Hz); IR (KBr) 3343, 3164, 1661, 1628, 1561, 1424, 1389, 1125. Anal. (C7H6INO) C, H, N. 3-Iodo-benzamide was prepared 2 h Solvent was removed the brown oily residue was dissolved in THF (50 mL) added to a solution of 18% aqueous NH4OH (260 mL) at 0° C After stirring the mixture for 15 min the liquid was decanted off The white solid was collected by filtration washed with water dried under vacuum

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

Procedure: A solution of 3-iodobenzamide (I29) (1.65 g, 6.66 mmol), Cu(I)I (127 mg, 0.666 mmol) and triphenylphosphine (524 mg, 2.00 mmol) in THF (100 mL) and triethylamine (4.64 mL, 33.3 mmol) was sonicated for 10 minutes under a nitrogen atmosphere. PdCl2(PPh3)2 (642 mg, 0.67 mmol) and TMS acetylene (1.88 mL, 13.3 mmol) were then added and the reaction stirred at room temperature for 3 days. The volatiles were evaporated in vacuo and the residue chromatographed on silica gel (0-50% ethyl acetate/petroleum benzine 40-60° C.) to give the title compound (I30) (1.53 g); 1H NMR (400 MHz, CDCl3) δ 7.78 (t, J=1.5 Hz, 1H), 7.67 (ddd, J=7.8, 1.8, 1.2 Hz, 1H), 7.53-7.48 (m, 1H), 7.29 (td, J=7.8, 0.5 Hz, 1H), 0.15 (s, 9H). The volatiles were evaporated in vacuo the residue chromatographed on silica gel (0-50% ethyl acetate/petroleum benzine 40-60° C.)

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

Procedure: A solution of 3-iodobenzamide (I29) (1.65 g, 6.66 mmol), Cu(I)I (127 mg, 0.666 mmol) and triphenylphosphine (524 mg, 2.00 mmol) in THF (100 mL) and triethylamine (4.64 mL, 33.3 mmol) was sonicated for 10 minutes under a nitrogen atmosphere. PdCl2(PPh3)2 (642 mg, 0.67 mmol) and TMS acetylene (1.88 mL, 13.3 mmol) were then added and the reaction stirred at room temperature for 3 days. The volatiles were evaporated in vacuo and the residue chromatographed on silica gel (0-50% ethyl acetate/petroleum benzine 40-60° C.) to give the title compound (I30) (1.53 g); 1H NMR (400 MHz, CDCl3) δ 7.78 (t, J=1.5 Hz, 1H), 7.67 (ddd, J=7.8, 1.8, 1.2 Hz, 1H), 7.53-7.48 (m, 1H), 7.29 (td, J=7.8, 0.5 Hz, 1H), 0.15 (s, 9H). The volatiles were evaporated in vacuo the residue chromatographed on silica gel (0-50% ethyl acetate/petroleum benzine 40-60° C.)

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

Procedure: To a stirred solution of 3-iodobenzoic acid (2.00 g, 8.06 mmol) and DIPEA (562 mL, 32.3 mmol) in MeCN (100 mL) at room temperature was added HOBT (1.63 g, 12.1 mmol) and EDCI.HCl (2.32 g, 12.1 mmol). After stirring for 10 minutes, ammonium carbonate (4.65 g, 48.4 mmol) was added and the resulting solution was stirred overnight. The volatiles were removed in vacuo to yield a crude solid which was suspended in water (100 mL). The resulting suspension was sonicated for 10 minutes then the solid collected by filtration. The filter cake was washed with water (20 mL) and dried to yield the title compound (I29) (1.65 g 83%) as a brown solid; 1H NMR (400 MHz, CDCl3) δ 8.13 (t, J=1.6 Hz, 1H), 7.83 (ddd, J=7.9, 1.7, 1.1 Hz, 1H), 7.73 (ddd, J=7.8, 1.7, 1.1 Hz, 1H), 7.16 (t, J=7.8 Hz, 1H), 6.18-5.49 (m, J=137.3 Hz, 2H). LCMS Method C: rt=5.04 min; m/z=248 [M+1]+. the resulting solution was stirred overnight The volatiles were removed in vacuo to yield a crude solid which The resulting suspension was sonicated for 10 minutes the solid collected by filtration The filter cake was washed with water (20 mL) dried

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

Procedure: A mixture of 3-iodobenzamide (500 mg, 2.0 mmol) in toluene (5 mL) was treated with Lawesson's reagent (404 mg, 1 mmol) and the mixture heated at reflux for 16 hours. After cooling, silica gel chromatography afforded 260 mg (99% yield) of 3-iodothiobenzamide, as a yellow solid. the mixture heated at reflux for 16 hours After cooling

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

Procedure: A suspension of 3-iodobenzoic acid (4.04 g, 16.2 mmol) in dichloromethane (30 mL) was treated with 2M oxalyl chloride (16 mL, 32 mmol, hexane) followed by two drops of N,N-dimethylformamide and stirred at ambient temperature for 2 hours. After this time the solvent was removed in vacuo and the residue dissolved in tetrahydrofuran (30 ml). The solution was cooled to 0° C. and treated with 2M ammonia (20 mL, 40 mmol, methanol) and the mixture stirred for 30 minutes. The mixture was then filtered and the solvent removed in vacuo. Recrystallization of the residue from methanol afforded 3.5 g (87%) of 3-iodobenzamide, as a white solid. After this time the solvent was removed in vacuo the residue dissolved in tetrahydrofuran (30 ml) The solution was cooled to 0° C. the mixture stirred for 30 minutes The mixture was then filtered the solvent removed in vacuo Recrystallization of the residue from methanol