5-chloro-2,4-dimethoxyaniline

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

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

Procedure: A mixture of 40 g. (0.184 m.) of the compound of Example I, C., 346 g. (0.184 m.) of 5-chloro-2,4-dimethoxyaniline and 500 ml. of ethanol was refluxed with stirring overnight. The solvents were removed by distillation and the crude product dissolved in 3000 ml. of MeOH. The MeOH filtrate was concentrated to one-half its volume, chilled and filtered to yield 13 g. m.p. 400°. A mixture of 40 g The solvents were removed by distillation the crude product dissolved in 3000 ml The MeOH filtrate was concentrated to one-half its volume chilled filtered to yield 13 g

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

Procedure: A mixture of 40 g. (0.184 m.) of the compound of Example I, C., 346 g. (0.184 m.) of 5-chloro-2,4-dimethoxyaniline and 500 ml. of ethanol was refluxed with stirring overnight. The solvents were removed by distillation and the crude product dissolved in 3000 ml. of MeOH. The MeOH filtrate was concentrated to one-half its volume, chilled and filtered to yield 13 g. m.p. 400°. A mixture of 40 g The solvents were removed by distillation the crude product dissolved in 3000 ml The MeOH filtrate was concentrated to one-half its volume chilled filtered to yield 13 g

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

Procedure: The title compound was prepared in substantially the same manner as described in Example 16, from 5-chloro-2,4-dimethoxyaniline, and 4-methoxybenzoyl chloride and was obtained as an off-white solid, m.p. 254-256° C.; MS m/e 262 (M+H)+. was obtained as an off-white solid, m.p. 254-256° C.

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

Procedure: The title compound was prepared in substantially the same manner as described in Example 16, from 5-chloro-2,4-dimethoxyaniline, and 4-methoxybenzoyl chloride and was obtained as an off-white solid, m.p. 254–256° C.; MS. m/e 262 (M+H)+. was obtained as an off-white solid, m.p. 254–256° C.

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

Procedure: The title compound was prepared in substantially the same manner as described in Example 16, from 5-chloro-2,4-dimethoxyaniline, and 4-methoxybenzoyl chloride and was obtained as an off-white solid, m.p. 254-256° C.; MS m/e 262 (M+H)+. was obtained as an off-white solid, m.p. 254-256° C.

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

Procedure: The title compound was prepared in substantially the same manner as described in Example 16, from 5-chloro-2,4-dimethoxyaniline, and 4-methoxybenzoyl chloride and was obtained as an off-white solid, m.p. 254-256° C.; MS m/e 262 (M+H)+. was obtained as an off-white solid, m.p. 254-256° C.

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

Procedure: A mixture of (3-methoxycarbonylmethyl-2-oxo-3,4-dihydro-2H-quinazolin-1-yl)-acetic acid (Intermediate J) (395 mg, 1.078 mmol), HATU (594 mg, 1.186 mmol) and 5-chloro-2,4-dimethoxy-phenylamine (293 mg, 1.186 mmol) in DCM (5 ml) is treated with DIPEA (2.5 eq, 618 μL). The reaction solution is stirred at RT and after 24 hours the reaction mixture is diluted with 1 M HCl (5 ml) and extracted with DCM (2×15 ml). The combined separated organic layers are washed with aqueous saturated NaHCO3. The organic phase is dried over MgSO4, filtered and is concentrated in vacuo to afford the title compound as off-white solid; [M+H]+ 448. extracted with DCM (2×15 ml) The combined separated organic layers are washed with aqueous saturated NaHCO3 The organic phase is dried over MgSO4 filtered is concentrated in vacuo

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

Procedure: A mixture of (3-methoxycarbonylmethyl-2-oxo-3,4-dihydro-2H-quinazolin-1-yl)-acetic acid (Intermediate J) (395 mg, 1.078 mmol), HATU (594 mg, 1.186 mmol) and 5-chloro-2,4-dimethoxy-phenylamine (293 mg, 1.186 mmol) in DCM (5 ml) is treated with DIPEA (2.5 eq, 618 μL). The reaction solution is stirred at RT and after 24 hours the reaction mixture is diluted with 1 M HCl (5 ml) and extracted with DCM (2×15 ml). The combined separated organic layers are washed with aqueous saturated NaHCO3. The organic phase is dried over MgSO4, filtered and is concentrated in vacuo to afford the title compound as off-white solid; [M+H]+ 448. extracted with DCM (2×15 ml) The combined separated organic layers are washed with aqueous saturated NaHCO3 The organic phase is dried over MgSO4 filtered is concentrated in vacuo

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

Procedure: A cooled (0° C.) solution of 5-chloro-2,4-dimethoxyaniline (5 g) in DCM under an atmosphere of argon is treated dropwise with bromoacetyl bromide (2.4 ml). After 5 minutes, TEA (7.5 ml) is added dropwise and after stirring for 20 minutes the reaction mixture is diluted with water and extracted with DCM). The organic phase is washed with distilled water, dried over Na2SO4, filtered and evaporated to give a beige solid. This is purified by flash column chromatography on silica, eluting with 20-100% n-hexane in DCM to afford the title compound. [M+H]+ 308. extracted with DCM) The organic phase is washed with distilled water dried over Na2SO4 filtered evaporated to give a beige solid This is purified by flash column chromatography on silica eluting with 20-100% n-hexane in DCM

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

Procedure: A cooled (0° C.) solution of 5-chloro-2,4-dimethoxyaniline (5 g) in DCM under an atmosphere of argon is treated dropwise with bromoacetyl bromide (2.4 ml). After 5 minutes, TEA (7.5 ml) is added dropwise and after stirring for 20 minutes the reaction mixture is diluted with water and extracted with DCM). The organic phase is washed with distilled water, dried over Na2SO4, filtered and evaporated to give a beige solid. This is purified by flash column chromatography on silica, eluting with 20-100% n-hexane in DCM to afford the title compound. [M+H]+ 308. extracted with DCM) The organic phase is washed with distilled water dried over Na2SO4 filtered evaporated to give a beige solid This is purified by flash column chromatography on silica eluting with 20-100% n-hexane in DCM

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

Procedure: This compound is made analogously to Example 1-2 by replacing Intermediate A with [3-(2-tert-butoxycarbonylamino-ethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetic acid and by replacing cyclopentylamine with 5-chloro-2,4-dimethoxyaniline to afford the title compound. The reaction is carried out in DCM.