methyl 2-amino-5-iodobenzoate

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 5-iodoanthranilic acid methyl ester (1.00 g) and triethylamine (1.01 mL) in CH2Cl2 (25 mL) is added methanesulfonyl chloride (0.59 mL) at 0° C. The ice bath is removed and after 3 h at room temperature the solution is poured into water (20 mL) and extracted with CH2Cl2 (2×20 mL). The organic layers are combined, dried over MgSO4 and the solvent removed in vacuo. The resulting residue is dissolved in CH3OH (20 mL) and sodium methoxide (20 mL) is added. After 45 min, the solvent is removed in vacuo. The residue is diluted with Et2O (20 mL) and washed with water (20 mL). The organic layer is separated, dried over MgSO4, filtered, and concentrated in vacuo. The crude black liquid is purified by silica gel column chromatography (4/1, hexanes/EtOAc ) to afford 0.58g (46%) of the title compound as a brown solid. Physical characteristics: m.p. 119-120° C.; 1H NMR (300 MHz, CDCl3) δ 10.41, 8.36, 7.82, 7.52, 3.94, 3.06; IR (diffuse reflectance) 1700, 1682, 1483, 1385, 1335, 1328, 1307, 1249, 1213, 1159, 1147, 1093, 1086, 978, 971 cm−1; MS (FAB) m/z 356 (MH+); HRMS (FAB) m/z 355.9447 (C9H10INO4S+H). Anal. Found: C, 30.49; H, 2.88; N, 3.96. The ice bath is removed and after 3 h at room temperature the solution is poured into water (20 mL) extracted with CH2Cl2 (2×20 mL) dried over MgSO4 the solvent removed in vacuo The resulting residue is dissolved in CH3OH (20 mL) sodium methoxide (20 mL) is added the solvent is removed in vacuo The residue is diluted with Et2O (20 mL) washed with water (20 mL) The organic layer is separated dried over MgSO4 filtered concentrated in vacuo The crude black liquid is purified by silica gel column chromatography (4/1, hexanes/EtOAc )

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

Procedure: To a solution of 5-iodoanthranilic acid methyl ester (1.00 g) and triethylamine (1.01 mL) in CH2Cl2 (25 mL) is added methanesulfonyl chloride (0.59 ml) at 0° C. The ice bath is removed and after 3 h at room temperature the solution is poured into water (20 mL) and extracted with CH2Cl2 (2×20 mL). The organic layers are combined, dried over MgSO4 and the solvent removed in vacuo. The resulting residue is dissolved in CH3OH (20 mL) and sodium methoxide (20 mL) is added. After 45 min, the solvent is removed in vacuo. The residue is diluted with Et2O (20 mL) and washed with water (20 mL). The organic layer is separated, dried over MgSO4, filtered, and concentrated in vacuo. The crude black liquid is purified by silica gel column chromatography (4/1, hexanes/EtOAc) to afford 0.58 g (46%) of the title compound as a brown solid. Physical characteristics: m.p. 119-120° C.; 1H NMR (300 MHz, CDCl3) δ10.41, 8.36, 7.82, 7.52, 3.94, 3.06; IR (diffuse reflectance) 1700, 1682, 1483, 1385, 1335, 1328, 1307, 1249, 1213, 1159, 1147, 1093, 1086, 978, 971 cm−1; MS (FAB) m/z 356 (MH+); HRMS (FAB) m/z 355.9447 (C9H10INO4S+H). Anal. Found: C, 30.49; H, 2.88; N, 3.96. The ice bath is removed and after 3 h at room temperature the solution is poured into water (20 mL) extracted with CH2Cl2 (2×20 mL) dried over MgSO4 the solvent removed in vacuo The resulting residue is dissolved in CH3OH (20 mL) sodium methoxide (20 mL) is added the solvent is removed in vacuo The residue is diluted with Et2O (20 mL) washed with water (20 mL) The organic layer is separated dried over MgSO4 filtered concentrated in vacuo The crude black liquid is purified by silica gel column chromatography (4/1, hexanes/EtOAc)

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

Procedure: A solution of diisobutylaluminium hydride (210 cm3 of a 1.5M solution in THF) was added at -30° to a stirred solution of methyl-2-amino-5-iodobenzoate (28.0 g) in THF (100 cm3) under nitrogen. The mixture was warmed to room temperature, stirred for 16 hours and treated with methanol (35 cm3). Ethyl acetate (500 cm3) was added and the mixture filtered to remove inorganic material. The filtrate was concentrated in vacuo to afford a solid which was chromatographed on silica (Merck "MK 60.9385") eluting wiht chloroform:methanol, 49:1 (by volume), and the requisite fractions were combined and evaporated in vacuo to give 2-amino-5-iodobenzyl alcohol, m.p. 125°, (19.0 g). the mixture filtered to remove inorganic material The filtrate was concentrated in vacuo to afford a solid which was chromatographed on silica (Merck "MK 60.9385") eluting wiht chloroform evaporated in vacuo

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

Procedure: A solution of diisobutylaluminium hydride (210 cm3 of a 1.5M solution in THF) was added at -30° to a stirred solution of methyl-2-amino-5-iodobenzoate (28.0 g) in THF (100 cm3) under nitrogen. The mixture was warmed to room temperature, stirred for 16 hours and treated with methanol (35 cm3). Ethyl acetate (500 cm3) was added and the mixture filtered to remove inorganic material. The filtrate was concentrated in vacuo to afford a solid which was chromatographed on silica (Merck "MK 60.9385") eluting wiht chloroform:methanol, 49:1 (by volume), and the requisite fractions were combined and evaporated in vacuo to give 2-amino-5-iodobenzyl alcohol, m.p. 125°, (19.0 g). the mixture filtered to remove inorganic material The filtrate was concentrated in vacuo to afford a solid which was chromatographed on silica (Merck "MK 60.9385") eluting wiht chloroform evaporated in vacuo

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

Procedure: Methyl 2-amino-5-iodobenzoate (17.8 g, 64 mmol) was heated in 300 mL of formamide at 190° C. for 2 hours. The mixture was cooled to room temperature and the solid product was filtrated and dried in vacuum. The formed product 1403-174 was used without further purification. (10 g, 56.1%): LC-MS: 273 [M+1]+, 1H NMR (DMSO-d6): δ 7.46 (d, J=9.0 Hz, 1H), 8.10 (m, 2H), 8.36 (d, J=2.1 Hz, 1 H), 12.40 (s, 1H). the solid product was filtrated dried in vacuum The formed product 1403-174 was used without further purification

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

Procedure: Methyl 2-amino-5-iodobenzoate (17.8 g, 64 mmol) was heated in 300 mL of formamide at 190° C. for 2 hours. The mixture was cooled to room temperature and the solid product was filtrated and dried in vacuum. The formed product 1403-174 was used without further purification. (10 g, 56.1%): LC-MS: 273 [M+1]+, 1H NMR (DMSO-d6): δ 7.46 (d, J=9.0 Hz, 1H), 8.10 (m, 2H), 8.36 (d, J=2.1 Hz, 1 H), 12.40 (s, 1H). the solid product was filtrated dried in vacuum The formed product 1403-174 was used without further purification

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

Procedure: To methyl 2-amino-5-iodobenzoate (i-a) (15 g, 54 mmol) was added 200 mL of CH2Cl2, followed by DIEA (9.4 mL, 54 mmol) and a catalytic amount of DMAP. Ethyl 4-chloro-4-oxobutanoate (Rc═Rd═H) (8.5 mL, 60 mmol) was added, and the reaction mixture was allowed to stir at room temperature overnight. The reaction mixture was then poured into 250 mL H2O, and the organic layer was washed with brine, dried over MgSO4, filtered, and concentrated in vacuo to afford ii-a (22 g, 99%) as a pale yellow solid: MS m/z=406 (M+H). the organic layer was washed with brine dried over MgSO4 filtered concentrated in vacuo to afford ii-a (22 g, 99%) as a pale yellow solid

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

Procedure: To a solution of 5-iodoanthranilic acid methyl ester (1.00 g) and triethylamine (1.01 mL) in CH2Cl2 (25 mL) is added methanesulfonyl chloride (0.59 mL) at 0° C. The ice bath is removed and after 3 h at room temperature the solution is poured into water (20 mL) and extracted with CH2Cl2 (2×20 mL). The organic layers are combined, dried over MgSO4 and the solvent removed in vacuo. The resulting residue is dissolved in CH3OH (20 mL) and sodium methoxide (20 mL) is added. After 45 min, the solvent is removed in vacuo. The residue is diluted with Et2O (20 mL) and washed with water (20 mL). The organic layer is separated, dried over MgSO4, filtered, and concentrated in vacuo. The crude black liquid is purified by silica gel column chromatography (4/1, hexanes/EtOAc ) to afford 0.58g (46%) of the title compound as a brown solid. Physical characteristics: m.p. 119-120° C.; 1H NMR (300 MHz, CDCl3) δ 10.41, 8.36, 7.82, 7.52, 3.94, 3.06; IR (diffuse reflectance) 1700, 1682, 1483, 1385, 1335, 1328, 1307, 1249, 1213, 1159, 1147, 1093, 1086, 978, 971 cm−1; MS (FAB) m/z 356 (MH+); HRMS (FAB) m/z 355.9447 (C9H10INO4S+H). Anal. Found: C, 30.49; H, 2.88; N, 3.96. The ice bath is removed and after 3 h at room temperature the solution is poured into water (20 mL) extracted with CH2Cl2 (2×20 mL) dried over MgSO4 the solvent removed in vacuo The resulting residue is dissolved in CH3OH (20 mL) sodium methoxide (20 mL) is added the solvent is removed in vacuo The residue is diluted with Et2O (20 mL) washed with water (20 mL) The organic layer is separated dried over MgSO4 filtered concentrated in vacuo The crude black liquid is purified by silica gel column chromatography (4/1, hexanes/EtOAc )

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Methyl 2-amino-5-iodobenzoate (17.8 g, 64 mmol) was heated in 300 mL of formamide at 190° C. for 2 hours. The mixture was cooled to room temperature and the solid product was filtrated and dried in vacuum. The formed product 1403-174 was used without further purification. (10 g, 56.1%): LC-MS: 273 [M+1]+, 1H NMR (DMSO-d6): δ 7.46 (d, J=9.0 Hz, 1H), 8.10 (m, 2H), 8.36 (d, J=2.1 Hz, 1 H), 12.40 (s, 1H). the solid product was filtrated dried in vacuum The formed product 1403-174 was used without further purification

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

Procedure: To methyl 2-amino-5-iodobenzoate (i-a) (15 g, 54 mmol) was added 200 mL of CH2Cl2, followed by DIEA (9.4 mL, 54 mmol) and a catalytic amount of DMAP. Ethyl 4-chloro-4-oxobutanoate (Rc═Rd═H) (8.5 mL, 60 mmol) was added, and the reaction mixture was allowed to stir at room temperature overnight. The reaction mixture was then poured into 250 mL H2O, and the organic layer was washed with brine, dried over MgSO4, filtered, and concentrated in vacuo to afford ii-a (22 g, 99%) as a pale yellow solid: MS m/z=406 (M+H). the organic layer was washed with brine dried over MgSO4 filtered concentrated in vacuo to afford ii-a (22 g, 99%) as a pale yellow solid