4-chloro-2,6-dimethylaniline

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

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

Procedure: A solution of 2.56 g of phenyl chloroformate in 20 ml of toluene was added to a cold solution of 2.47 g of 4-chloro-2,6-dimethylaniline and 2.4 ml of N,N-dimethylaniline in 80 ml of toluene. The resulting mixture was stirred at room temperature for 11/2 hours and then diluted with water The organic layer was washed with 3N hydrochloric acid, brine, dried, and evaporated. The residual solid was crystallized from ethylacetate:hexane to yield phenyl-N-(4-chloro-2,6-dimethylphenyl)carbamate, mp 158°-160° C. was washed with 3N hydrochloric acid, brine dried evaporated The residual solid was crystallized from ethylacetate

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

Procedure: The product of Example 162b (300 mg, 0.6197 mmol) and 4-Chloro-2,6-dimethyl-phenylamine (119 mg, 0.6197 mmol) were combined in toluene (10 mL) and reacted as in Example 162c to give the title compound that was used without further manipulation. reacted as in Example 162c

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

Procedure: A solution of 2.56 g of phenyl chloroformate in 20 ml of toluene was added to a cold solution of 2.47 g of 4-chloro-2,6-dimethylaniline and 2.4 ml of N,N-dimethylaniline in 80 ml of toluene. The resulting mixture was stirred at room temperature for 11/2 hours and then diluted with water The organic layer was washed with 3N hydrochloric acid, brine, dried, and evaporated. The residual solid was crystallized from ethylacetate:hexane to yield phenyl-N-(4-chloro-2,6-dimethylphenyl)carbamate, mp 158°-160° C. was washed with 3N hydrochloric acid, brine dried evaporated The residual solid was crystallized from ethylacetate

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

Procedure: A solution of 2.56 g of phenyl chloroformate in 20 ml of toluene was added to a cold solution of 2.47 g of 4-chloro-2,6-dimethylaniline and 2.4 ml of N,N-dimethylaniline in 80 ml of toluene. The resulting mixture was stirred at room temperature for 11/2 hours and then diluted with water The organic layer was washed with 3N hydrochloric acid, brine, dried, and evaporated. The residual solid was crystallized from ethylacetate:hexane to yield phenyl-N-(4-chloro-2,6-dimethylphenyl)carbamate, mp 158°-160° C. was washed with 3N hydrochloric acid, brine dried evaporated The residual solid was crystallized from ethylacetate

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

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

Procedure: To a suspended solution of 4-chloro-2,6-dimethylaniline (24.0 g) in toluene (300 mL) were added methyl acetoacetate (17.9 g) and p-toluenesulfonic acid monohydrate (293 mg) and the mixture was heated to reflux and stirred for 4 hours. The reaction mixture was concentrated. To the obtained residue was added diisopropyl ether and the insoluble matter which was precipitated was removed. The filtrate was concentrated. The obtained residue was purified by preparative medium pressure liquid chromatography W-prep 2XY (column: main column 3L, inject column L; automatic condition setting: hexane:ethyl acetate=9:1, preparative isolation mode GR) to give the title compound (24.7 g) having the following physical data. the mixture was heated to reflux The reaction mixture was concentrated To the obtained residue was added diisopropyl ether the insoluble matter which was precipitated was removed The filtrate was concentrated The obtained residue was purified by preparative medium pressure liquid chromatography W-prep 2XY (column: main column 3L, inject column L; automatic condition setting: hexane:ethyl acetate=9:1, preparative isolation mode GR)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an initial charge of 75 ml of 48% aqueous HBr are added, in portions, 19.67 g [0.12 mol] of 4-chloro-2,6-dimethylaniline. The resulting thick suspension is stirred at 80° C. for 15 minutes. Then the mixture is cooled to −10° C., and a solution of 9.6 g [0.139 mol] of NaNO2 in 45 ml of water is added dropwise within approx. 1 h at such a rate that the temperature does not exceed −5° C. 100 mg of sulphamic acid are added. Then the suspension of the diazonium salt, cooled to −10° C., is metered within about 35 minutes into a solution, heated to 80° C., of 17.93 g [0.125 mol] of Cu(I)Br in 75 ml of 62% aqueous HBr. The reaction mixture is then stirred at 80° C. for another 1 hour, allowed to cool to room temperature and admixed with 125 ml of water, the phases are separated and the aqueous phase is extracted three times with 50 ml each time of methylene chloride. The combined organic phases are washed twice with 25 ml each time of water, dried and concentrated under reduced pressure. This gives 20.2 g of an oil which, according to GC, contains 95.5% 4-chloro-2,6-dimethylbromobenzene (73% of theory). Then the mixture is cooled to −10° C. does not exceed −5° C cooled to −10° C. is metered within about 35 minutes into a solution The reaction mixture is then stirred at 80° C. for another 1 hour to cool to room temperature the phases are separated the aqueous phase is extracted three times with 50 ml each time of methylene chloride The combined organic phases are washed twice with 25 ml each time of water dried concentrated under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an initial charge of 65 ml of 48% aqueous HBr are added, in portions, 15.56 g [0.1 mol] of 4-chloro-2,6-dimethylaniline. The resulting thick suspension is stirred at 80° C. for 15 minutes. It is then cooled to −10° C., and a solution of 8 g [0.116 mol] of NaNO2 in 35 ml of water is added dropwise within approx. 40 minutes at such a rate that the temperature does not exceed −5° C. 80 mg of sulphamic acid are added. Then the suspension of the diazonium salt cooled to −10° C. is metered within about 25 minutes into a solution, heated to 80° C., of 28.6 g [0.103 mol] of FeSO4×7H20 in 65 ml of 62% aqueous HBr. The reaction mixture is then stirred at 80° C. for another 1 hour, allowed to cool to room temperature and admixed with 125 ml of water, the phases are separated and the aqueous phase is extracted three times with 50 ml each time of methylene chloride. The combined organic phases are washed twice with 25 ml each time of water, dried and concentrated under reduced pressure. This gives 17.2 g of an oil which, according to GC, contains 95.6% 4-chloro-2,6-dimethylbromobenzene (75% of theory). It is then cooled to −10° C. does not exceed −5° C cooled to −10° C. is metered within about 25 minutes into a solution The reaction mixture is then stirred at 80° C. for another 1 hour to cool to room temperature the phases are separated the aqueous phase is extracted three times with 50 ml each time of methylene chloride The combined organic phases are washed twice with 25 ml each time of water dried concentrated under reduced pressure

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

Procedure: The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 4-Chloro-2,6-dimethyl-aniline as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 8.73 (br, 1H), 7.72 (br, 1H), 7.19 (s, 2H), 7.03-6.95 (2H), 6.36 (br, 1H), 3.95 (t, 2H), 3.85 (s, 3H), 2.96 (t, 2H) and 2.18 (s, 6H); MS (ESI) (M+H)+ 382.

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

Procedure: A solution of 2.56 g of phenyl chloroformate in 20 ml of toluene was added to a cold solution of 2.47 g of 4-chloro-2,6-dimethylaniline and 2.4 ml of N,N-dimethylaniline in 80 ml of toluene. The resulting mixture was stirred at room temperature for 11/2 hours and then diluted with water. The organic layer was washed with 3N hydrochloric acid, brine, dried, and evaporated. The residual solid was crystallized from ethylacetate:hexane to yield phenyl-N-(4-chloro-2,6-dimethylphenyl)carbamate, mp 158°-160° C. The organic layer was washed with 3N hydrochloric acid, brine dried evaporated The residual solid was crystallized from ethylacetate

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

Procedure: The product of Example 162b (300 mg, 0.6197 mmol) and 4-Chloro-2,6-dimethyl-phenylamine (119 mg, 0.6197 mmol) were combined in toluene (10 mL) and reacted as in Example 162c to give the title compound that was used without further manipulation. reacted as in Example 162c