2-chloro-3-methylaniline

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: In the manner described in example 3, 2-bromophenylacetic acid is condensed with 2-chloro-3-methylaniline to yield 2-[(2-chloro-3-methylphenyl)amino]phenylacetic acid.

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

Procedure: In the manner described in example 3, 2-bromophenylacetic acid is condensed with 2-chloro-3-methylaniline to yield 2-[(2-chloro-3-methylphenyl)amino]phenylacetic acid.

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

Procedure: 2-Chloro-3-methylaniline was converted to the 2-chloro-3-methylformanilide according to Method A3a, Step 1. The formanilide was converted to 2-chloro-3-methylphenyl isocyanide dichloride according to Method A3a, Step 2. 1-Hydroxymethylcyclopentanamine HCl salt was synthesized according to Method B1c. The 2-hydroxyethylamine was converted to 13-aza-6-oxadispiro[4.2.4.I]tridecane according to Method B4d, Step 1. The oxazolidine was reductively opened according to Method B4d, Step 2 to give 1-(cyclopentylamino)-1-(hydroxymethyl)cyclopentane. The substituted 2-hydroxyethylamine was converted to 1-(cyclopentylamino)-1-(thioacetylmethyl)cyclopentane according to Method C6c, Step 1. The thioacetate was hydrolyzed according to Method C6c, Step 2 to give 1-(cyclopentylamino)-1-(thiomethyl)cyclopentane. The 2-thioethylamine was reacted with 2-chloro-3-methylphenyl isocyanide dichloride according to Method C6c to afford 2-(2-chloro-3-methylphenylimino)-1-cyclopentyl-3-thia-1-azaspiro[4.4]nonane.

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

Procedure: 2-Chloro-3-methylaniline was converted to the 2-chloro-3-methylformanilide according to Method A3a, Step 1. The formanilide was converted to 2-chloro-3-methylphenyl isocyanide dichloride according to Method A3a, Step 2. 1-Hydroxymethylcyclopentanamine HCl salt was synthesized according to Method B1c. The 2-hydroxyethylamine was converted to 13-aza-6-oxadispiro[4.2.4.I]tridecane according to Method B4d, Step 1. The oxazolidine was reductively opened according to Method B4d, Step 2 to give 1-(cyclopentylamino)-1-(hydroxymethyl)cyclopentane. The substituted 2-hydroxyethylamine was converted to 1-(cyclopentylamino)-1-(thioacetylmethyl)cyclopentane according to Method C6c, Step 1. The thioacetate was hydrolyzed according to Method C6c, Step 2 to give 1-(cyclopentylamino)-1-(thiomethyl)cyclopentane. The 2-thioethylamine was reacted with 2-chloro-3-methylphenyl isocyanide dichloride according to Method C6c to afford 2-(2-chloro-3-methylphenylimino)-1-cyclopentyl-3-thia-1-azaspiro[4.4]nonane.

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

Procedure: A mixture of 2-chloro-3-nitrotoluene (1.0 g, 5.8 mmol) and 5% platinum-on-carbon (0.1 g) in 25 ml of EtOH was reacted overnight at room temperature and 60 psi. The reaction mixture was filtered and the filtrate concentrated in vacuo to provide an oil. This oil was dissolved in EtOAc, washed with H2O, dried over Na2SO4, filtered and then concentrated in vacuo. was reacted overnight at room temperature The reaction mixture was filtered the filtrate concentrated in vacuo to provide an oil washed with H2O dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: To a mixture of 6.08 g of 2-chloro-3-methylaniline, 9 g of di(2-bromoethyl)amine hydrobromide and 4 ml of water was added a solution of 0.8 g of potassium hydorxide and 2.5 ml of water 3 times of 1 hour interval at 100° C., then the reaction mixture was stirred at the same temperature for 9 hours. To the resultant reaction mixture was added potassium hydroxide to make the mixture alkaline, and the mixture was extracted with diethyl ether, washed with water, dried with anhydrous magnesium sulfate. The solvent was removed by evaporation and the residue thus obtained was purified by means of a silica gel column chromatography (eluent: 5%-methanol/chloroform), and obtained 3.41 g of 4-(2-chloro-3-methylphenyl)piperazine. To the resultant reaction mixture the mixture was extracted with diethyl ether washed with water dried with anhydrous magnesium sulfate The solvent was removed by evaporation the residue thus obtained was purified by means of a silica gel column chromatography (eluent: 5%-methanol/chloroform)

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

Procedure: To a mixture of 6.08 g of 2-chloro-3-methylaniline, 9 g of di(2-bromoethyl)amine hydrobromide and 4 ml of water was added a solution of 0.8 g of potassium hydorxide and 2.5 ml of water 3 times of 1 hour interval at 100° C., then the reaction mixture was stirred at the same temperature for 9 hours. To the resultant reaction mixture was added potassium hydroxide to make the mixture alkaline, and the mixture was extracted with diethyl ether, washed with water, dried with anhydrous magnesium sulfate. The solvent was removed by evaporation and the residue thus obtained was purified by means of a silica gel column chromatography (eluent: 5%-methanol/chloroform), and obtained 3.41 g of 4-(2-chloro-3-methylphenyl)piperazine. To the resultant reaction mixture the mixture was extracted with diethyl ether washed with water dried with anhydrous magnesium sulfate The solvent was removed by evaporation the residue thus obtained was purified by means of a silica gel column chromatography (eluent: 5%-methanol/chloroform)

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

Procedure: In the manner described in example 3, 2-bromophenylacetic acid is condensed with 2-chloro-3-methylaniline to yield 2-[(2-chloro-3-methylphenyl)amino]phenylacetic acid.

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

Procedure: 2-Chloro-3-methylaniline was converted to the 2-chloro-3-methylformanilide according to Method A3a, Step 1. The formanilide was converted to 2-chloro-3-methylphenyl isocyanide dichloride according to Method A3a, Step 2. 1-Hydroxymethylcyclopentanamine HCl salt was synthesized according to Method B1c. The 2-hydroxyethylamine was converted to 13-aza-6-oxadispiro[4.2.4.I]tridecane according to Method B4d, Step 1. The oxazolidine was reductively opened according to Method B4d, Step 2 to give 1-(cyclopentylamino)-1-(hydroxymethyl)cyclopentane. The substituted 2-hydroxyethylamine was converted to 1-(cyclopentylamino)-1-(thioacetylmethyl)cyclopentane according to Method C6c, Step 1. The thioacetate was hydrolyzed according to Method C6c, Step 2 to give 1-(cyclopentylamino)-1-(thiomethyl)cyclopentane. The 2-thioethylamine was reacted with 2-chloro-3-methylphenyl isocyanide dichloride according to Method C6c to afford 2-(2-chloro-3-methylphenylimino)-1-cyclopentyl-3-thia-1-azaspiro[4.4]nonane.