4-fluoro-2-methoxyaniline

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

Procedure: To 4-fluoro-2-methoxyaniline (370 mg, 2.62 mmol) in refluxing 6N HCl (5 mL) was added dropwise (E)-but-2-enal (367 mg, 5.24 mmol). The reaction was heated to reflux for 2 hours then cooled and neutralized with NH4OH. The aqueous phase was extracted with DCM, and the combined organic phases dried over MgSO4 and concentrated to yield 6-fluoro-8-methoxy-2-methylquinoline (500 mg, 99.8% yield) as a brown solid. The reaction was heated to reflux for 2 hours then cooled The aqueous phase was extracted with DCM the combined organic phases dried over MgSO4 concentrated

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction mixture of 4-fluoro-2-methoxy-aniline(0.155 g, 1.10 mmol), 5,6-dimethyl-2-chloro4-(1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine(0.24 lg, 0.84 mmol), triethylamine(0.15 ml, 1.1 mmol) and propyleneglycol (2 ml) was heated to 140° C. for 5 hours, cooled to a room temperature, diluted with dichloromethane(10 ml), and then washed with water. The separated organic layer was concentrated and the residual oil was purified by column chromatography(ethylacetate/N-hexane=1/1) to give 0.247 g of the titled compound. (Yield 75.2%) cooled to a room temperature washed with water The separated organic layer was concentrated the residual oil was purified by column chromatography(ethylacetate/N-hexane=1/1)

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction mixture of 4-fluoro-2-methoxy-aniline(0.155 g, 1.10 mmol), 5,6-dimethyl-2-chloro4-(1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine(0.24 lg, 0.84 mmol), triethylamine(0.15 ml, 1.1 mmol) and propyleneglycol (2 ml) was heated to 140° C. for 5 hours, cooled to a room temperature, diluted with dichloromethane(10 ml), and then washed with water. The separated organic layer was concentrated and the residual oil was purified by column chromatography(ethylacetate/N-hexane=1/1) to give 0.247 g of the titled compound. (Yield 75.2%) cooled to a room temperature washed with water The separated organic layer was concentrated the residual oil was purified by column chromatography(ethylacetate/N-hexane=1/1)

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

Procedure: Paladium/carbon(Pd/C, 5%, 0.5 g) was added to a solution of 4-fluoro-2-methoxynitrobenzene (1.65 g, 9.6 mmol) in ethanol, which was then stirred for 1 hour under 30 psi of hydrogen pressure. The reaction mixture was filtered to remove paladium/carbon, and concentrated to give 1.35 g of the titled compound. (Yield 100%) The reaction mixture was filtered to remove paladium/carbon concentrated

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

Procedure: Paladium/carbon(Pd/C, 5%, 0.5 g) was added to a solution of 4-fluoro-2-methoxynitrobenzene (1.65 g, 9.6 mmol) in ethanol, which was then stirred for 1 hour under 30 psi of hydrogen pressure. The reaction mixture was filtered to remove paladium/carbon, and concentrated to give 1.35 g of the titled compound. (Yield 100%) The reaction mixture was filtered to remove paladium/carbon concentrated

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

Procedure: The product is prepared according to the procedure described in Example 5, using 250 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate and 460 mg of 4-fluoro-2-methoxyaniline in place of the 2,4-difluoroaniline. 245 mg of N-(4-fluoro-2-methoxyphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide are obtained in the form of a pinkish solid, the characteristics of which are the following: The product is prepared

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

Procedure: 4-Chloro-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester (15.0 g), 4-fluoro-2-methoxyaniline (9.5 g), 4M hydrochloric acid in dioxane (4.5 ml) and dioxane (100.0 ml) were stirred at 100° C. overnight. Then the mixture was filtrated and the solid was dried in vacuo. Then the mixture was filtrated the solid was dried in vacuo

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

Procedure: When 4-fluoroaniline and 2-methyl-nitrobenzene are used in the above example in place of 4-fluoro-2-methoxyaniline and nitrobenzene there is obtained 4'-fluoro-3-methyl-4-nitrobiphenyl.

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

Procedure: A mixture of 7.7 grams of 4-fluoro-2-methoxyaniline, 200 ml. of nitrobenzene, and 9.0 grams of isoamyl nitrite, is warmed on the steam bath until a vigorous reaction with evolution of gas sets in. This evolution is allowed to proceed without heating until it has subsided, and the mixture is then heated on the steam bath for an additional 3 hours. The excess of nitrobenzene is removed in vacuo. The residue is purified for the desired isomer by elution from a silica gel column using petroleum-benzin to yield 4'-fluoro-2'-methoxy-4-nitrobiphenyl. without heating until it the mixture is then heated on the steam bath for an additional 3 hours The excess of nitrobenzene is removed in vacuo The residue is purified for the desired isomer by elution from a silica gel column

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

Procedure: A mixture of 7.7 grams of 4-fluoro-2-methoxyaniline, 200 ml. of nitrobenzene, and 9.0 grams of isoamyl nitrite, is warmed on the steam bath until a vigorous reaction with evolution of gas sets in. This evolution is allowed to proceed without heating until it has subsided, and the mixture is then heated on the steam bath for an additional 3 hours. The excess of nitrobenzene is removed in vacuo. The residue is purified for the desired isomer by elution from a silica gel column using petroleum-benzin to yield 4'-fluoro-2'-methoxy-4-nitrobiphenyl. without heating until it the mixture is then heated on the steam bath for an additional 3 hours The excess of nitrobenzene is removed in vacuo The residue is purified for the desired isomer by elution from a silica gel column

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

Procedure: To 4-fluoro-2-methoxyaniline (370 mg, 2.62 mmol) in refluxing 6N HCl (5 mL) was added dropwise (E)-but-2-enal (367 mg, 5.24 mmol). The reaction was heated to reflux for 2 hours then cooled and neutralized with NH4OH. The aqueous phase was extracted with DCM, and the combined organic phases dried over MgSO4 and concentrated to yield 6-fluoro-8-methoxy-2-methylquinoline (500 mg, 99.8% yield) as a brown solid. The reaction was heated to reflux for 2 hours then cooled The aqueous phase was extracted with DCM the combined organic phases dried over MgSO4 concentrated

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

Procedure: To 4-fluoro-2-methoxyaniline (370 mg, 2.62 mmol) in refluxing 6N HCl (5 mL) was added dropwise (E)-but-2-enal (367 mg, 5.24 mmol). The reaction was heated to reflux for 2 hours then cooled and neutralized with NH4OH. The aqueous phase was extracted with DCM, and the combined organic phases dried over MgSO4 and concentrated to yield 6-fluoro-8-methoxy-2-methylquinoline (500 mg, 99.8% yield) as a brown solid. The reaction was heated to reflux for 2 hours then cooled The aqueous phase was extracted with DCM the combined organic phases dried over MgSO4 concentrated