2-amino-6-methoxybenzamide

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: Using General Protocol II with 2,4-dichloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidine (3.00 g, 8.8 mmol) and 2-amino-6-(methyloxy)benzamide (3.10 g, 18.7 mmol), 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-(methyloxy)benzamide was isolated as white solid (1.15 g, 28% Yield); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.34 (s, 3 H), 3.81 (s, 3 H), 6.55 (s, 1 H), 6.94 (d, J=7.87 Hz, 1 H), 7.37-7.49 (m, 4 H), 7.63 (d, J=4.03 Hz, 3 H), 7.94 (d, J=8.24 Hz, 2 H), 10.98 (s, 1 H).

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-amino-6-methoxy-benzamide (1.00 g, 6.01 mmol) and 4-(2-hydroxy-ethoxy)-3,5-dimethyl-benzaldehyde (1.28 g, 6.59 mmol) in N,N-dimethylacetamide (15 mL) were added NaHSO3 (58.5 wt %, 0.68 g, 6.50 mmol) and p-TSA (0.23 g, 1.20 mmol) and the reaction mixture was heated at 115° C. for 20 hours, and cooled to room temperature. N,N-dimethylacetamide was removed under reduced pressure. The residue was diluted with water (50 mL), stirred for 30 minutes, and then filtered. The solid was suspended in dichloromethane (30 mL), stirred for 1 h, filtered, and dried under vacuum to give 2-[4-(2-hydroxy-ethoxy)-3,5-dimethyl-phenyl]-5-methoxy-3H-quinazolin-4-one as an off-white solid. Yield: 1.1 g (55%). cooled to room temperature N,N-dimethylacetamide was removed under reduced pressure The residue was diluted with water (50 mL) filtered stirred for 1 h filtered dried under vacuum

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-amino-6-methoxy-benzamide (1.00 g, 6.01 mmol) and 4-(2-hydroxy-ethoxy)-3,5-dimethyl-benzaldehyde (1.28 g, 6.59 mmol) in N,N-dimethylacetamide (15 mL) were added NaHSO3 (58.5 wt %, 0.68 g, 6.50 mmol) and p-TSA (0.23 g, 1.20 mmol) and the reaction mixture was heated at 115° C. for 20 hours, and cooled to room temperature. N,N-dimethylacetamide was removed under reduced pressure. The residue was diluted with water (50 mL), stirred for 30 minutes, and then filtered. The solid was suspended in dichloromethane (30 mL), stirred for 1 h, filtered, and dried under vacuum to give 2-[4-(2-hydroxy-ethoxy)-3,5-dimethyl-phenyl]-5-methoxy-3H-quinazolin-4-one as an off-white solid. Yield: 1.1 g (55%). cooled to room temperature N,N-dimethylacetamide was removed under reduced pressure The residue was diluted with water (50 mL) filtered stirred for 1 h filtered dried under vacuum

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

Procedure: To a stirred solution of 2-amino-6-methoxy-benzoic acid (3.00 g, 17.9 mmol) in THF (90 mL), EDCl (7.89 g, 41.1 mmol) and HOBt (7.95 g, 51.9 mmol) were added and stirred at room temperature for 30 minutes then N-methylmorpholine (6.15 g, 60.0 mmol) and aqueous 50% v/v NH4OH (12 mL, 171.4 mmol) was added. The mixture was stirred for 16 hours at room temperature. The solvent was removed under reduced pressure and the residue was extracted with ethylacetate (4×100 mL), the combined organic phase was washed with water and brine, and dried over anhydrous sodium sulfate; the solvent was evaporated to give 2-amino-6-methoxy-benzamide as an off-white solid. Yield: 1.90 g, (65%). The mixture was stirred for 16 hours at room temperature The solvent was removed under reduced pressure the residue was extracted with ethylacetate (4×100 mL) the combined organic phase was washed with water and brine dried over anhydrous sodium sulfate the solvent was evaporated

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 2-amino-6-methoxybenzamide (1.7 g) in methylene chloride (20 ml) is added pyridine (1.6 ml), and thereto is added dropwise acetoxyacetyl chloride (1.1 ml) which is cooled in an ice bath. The mixture is stirred at room temperature for 2 hours, and thereafter, the solvent is distilled off under reduced pressure. The resulting crude crystals are washed with water and then are recrystallized from ethanol to give the title compound (2.1 g) having the following physical properties. is cooled in an ice bath the solvent is distilled off under reduced pressure The resulting crude crystals are washed with water are recrystallized from ethanol

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

Procedure: To a solution of 2-amino-6-methoxybenzamide (1.7 g) in methylene chloride (20 ml) is added pyridine (1.6 ml), and thereto is added dropwise acetoxyacetyl chloride (1.1 ml) which is cooled in an ice bath. The mixture is stirred at room temperature for 2 hours, and thereafter, the solvent is distilled off under reduced pressure. The resulting crude crystals are washed with water and then are recrystallized from ethanol to give the title compound (2.1 g) having the following physical properties. is cooled in an ice bath the solvent is distilled off under reduced pressure The resulting crude crystals are washed with water are recrystallized from ethanol

Conditions: temp:3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Slow addition of 4.98 g. (0.03 mole) of 6-amino-o-anisamide to a mixture of 57% NaH (1.32 g., 0.0315 mole) in 50 ml. dimethylformamide was carried out at room temperature. After the evolution of H2 ceased, the mixture was cooled to 3° C. and 2.06 ml. (0.033 mole) of methyliodide was slowly added at 3°-5° C. The temperature was allowed to go up to room temperature and stir for 2 hours. The mixture was concentrated, the residue extracted into ethyl acetate-water, the mixture was basified, and the ethyl acetate layer was washed with water, brine and dried. Concentration gave a tan solid that was crystallized (ethanol), giving 0.45 g (8%) Of 6-amino-N-methyl-o-anisamide m.p. 186°-189° C. Slow addition of 4.98 g was carried out at room temperature to go up to room temperature The mixture was concentrated the residue extracted into ethyl acetate-water the ethyl acetate layer was washed with water, brine dried Concentration gave a tan solid that was crystallized (ethanol)

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

Procedure: Using General Protocol II with 2,4-dichloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidine (3.00 g, 8.8 mmol) and 2-amino-6-(methyloxy)benzamide (3.10 g, 18.7 mmol), 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-(methyloxy)benzamide was isolated as white solid (1.15 g, 28% Yield); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.34 (s, 3 H), 3.81 (s, 3 H), 6.55 (s, 1 H), 6.94 (d, J=7.87 Hz, 1 H), 7.37-7.49 (m, 4 H), 7.63 (d, J=4.03 Hz, 3 H), 7.94 (d, J=8.24 Hz, 2 H), 10.98 (s, 1 H).