2-chloro-6-methylbenzoyl chloride

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 test tube (25×150 mm) containing a stirring bar and 2-amino-indan-2-carboxylic acid ethyl ester (0.53 g, 2.58 mmol) is charged with dry DCM (3 mL). Stirring is initiated. After dissolution, the DIPEA (1.50 mL, 8.6 mmol) and 4-dimethylaminopyridine (2 mg, 17 μmol) are added. A solution of 2-chloro-6-methylbenzoyl chloride (5.8 mmol) in dry DCM (4 mL), as prepared above, is added to the reaction tube. After stirring for 18 h, tlc analysis (silica, 10% CH3OH in DCM) indicates complete consumption of the amine. The reaction mixture is diluted with DCM (10 mL) and washed with 5% aqueous HCl (2×5 mL) and brine (5 mL), dried over MgSO4 filtered and evaporated by pumping to constant weight gives 1.07 g of light brown solid. This material is purified by chromatography (silica, 2% to 20% EtOAc in DCM) on the ISCO Companion using a 40 g cartridge. Fractions 6-10 are combined, evaporated and pumped to yield a constant weight 550 mg of white amorphous solid. A test tube (25×150 mm) containing a stirring bar After dissolution is added to the reaction tube After stirring for 18 h consumption of the amine The reaction mixture is diluted with DCM (10 mL) washed with 5% aqueous HCl (2×5 mL) and brine (5 mL) dried over MgSO4 filtered evaporated

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

Procedure: A test tube (25×150 mm) containing a stirring bar and 2-amino-indan-2-carboxylic acid ethyl ester (0.53 g, 2.58 mmol) is charged with dry DCM (3 mL). Stirring is initiated. After dissolution, the DIPEA (1.50 mL, 8.6 mmol) and 4-dimethylaminopyridine (2 mg, 17 μmol) are added. A solution of 2-chloro-6-methylbenzoyl chloride (5.8 mmol) in dry DCM (4 mL), as prepared above, is added to the reaction tube. After stirring for 18 h, tlc analysis (silica, 10% CH3OH in DCM) indicates complete consumption of the amine. The reaction mixture is diluted with DCM (10 mL) and washed with 5% aqueous HCl (2×5 mL) and brine (5 mL), dried over MgSO4 filtered and evaporated by pumping to constant weight gives 1.07 g of light brown solid. This material is purified by chromatography (silica, 2% to 20% EtOAc in DCM) on the ISCO Companion using a 40 g cartridge. Fractions 6-10 are combined, evaporated and pumped to yield a constant weight 550 mg of white amorphous solid. A test tube (25×150 mm) containing a stirring bar After dissolution is added to the reaction tube After stirring for 18 h consumption of the amine The reaction mixture is diluted with DCM (10 mL) washed with 5% aqueous HCl (2×5 mL) and brine (5 mL) dried over MgSO4 filtered evaporated

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

Procedure: A round bottom flask containing the 2-chloro-6-methyl-benzoic acid (1.5 g, 8.79 mmol) and a stirring bar is charged with dry DCM (10 mL). Stirring is initiated. After several min, a solution of thionyl chloride (in DCM (2M), 6.6 mL, 13.2 mmol) is added via syringe. 2 drops of DMF are then added. The reaction immediately began to bubble gently. After 2 h bubbling ceases. After 3 h, the solvent is removed from the reaction mixture in vacuo. The oily residue is redissolved in DCM (6 mL) and the solvent once again removed in vacuo. The residue is dissolved in dry DCM (6 mL) and used without further purification in the next reaction sequence. The reaction to bubble gently After 2 h bubbling ceases the solvent is removed from the reaction mixture in vacuo The oily residue is redissolved in DCM (6 mL) the solvent once again removed in vacuo The residue is dissolved in dry DCM (6 mL) used without further purification in the next reaction sequence

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

Procedure: In one embodiment, the step comprises combining 2-chloro-6-methylbenzoyl chloride with aniline to afford 2-chloro-6-methyl-N-phenylbenzamide. In one embodiment, the step is optionally carried out in the presence of a base (e.g., an amine base such as Et3N).

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

Procedure: In one embodiment, the step comprises combining 2-chloro-6-methylbenzoyl chloride with aniline to afford 2-chloro-6-methyl-N-phenylbenzamide. In one embodiment, the step is optionally carried out in the presence of a base (e.g., an amine base such as Et3N).

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

Procedure: In one embodiment, the step comprises combining 2-chloro-6-methylbenzoic acid with, e.g., thionyl chloride or oxalyl chloride, optionally in the presence of a catalytic amount of DMF, to afford 2-chloro-6-methylbenzoyl chloride.

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

Procedure: N-[(2-chloro-6-methylphenyl)carbonyl]-4-(1,4-dimethyl-6-(trifluoromethyl)-2-oxo-3-pyridinyl)-L-phenylalanine was prepared from 4-[1,4-dimethyl-6-(trifluoromethyl)-2-oxo-3-pyridinyl]-L-phenylalanine methyl ester and 2-chloro-6-methylbenzoyl chloride using the general procedures described in example 44. ES-LRMS m/z 507.1 (M+H), 529.1 (M+Na).

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

Procedure: N-[(2-chloro-6-methylphenyl)carbonyl]-4-(1,4-dimethyl-6-(trifluoromethyl)-2-oxo-3-pyridinyl)-L-phenylalanine was prepared from 4-[1,4-dimethyl-6-(trifluoromethyl)-2-oxo-3-pyridinyl]-L-phenylalanine methyl ester and 2-chloro-6-methylbenzoyl chloride using the general procedures described in example 44. ES-LRMS m/z 507.1 (M+H), 529.1 (M+Na).

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

Procedure: N-[(2-chloro-6-methylphenyl)carbonyl]-4-(1,3,6-trimethyl-2,4-dioxo-5-pyrimidinyl)-L-phenylalanine 1-(acetoxy)ethyl ester was prepared from 4-(1,3,6-trimethyl-2,4-dioxo-5-pyrimidinyl)-L-phenylalanine 1-(acetoxy)ethyl ester and 2-chloro-6-methylbenzoyl chloride using the general procedures described in example 33 and was obtained as a white solid: mp 84-88° C. ES-HRMS m/e calcd for C28H30ClN3O7 (M+Na) 578.1664, found 578.1665. was obtained as a white solid