4-fluorobenzamide

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:

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: Following the general procedure for EXAMPLE 49 and making non-critical variations (-)-2-(isochroman-1-yl)ethanol (LXXIX, 0.394 g) and 4-(homopiperazin-1-yl)benzamide (IV; 0.601 g prepared by the method of EXAMPLE 47, Step 1 from 4-fluorobenzamide, III, and homopiperazine, II) are combined to give the title compound, mp 163.75-165°; MS (m/z) 379; [α]D -41° (c, 0.975, DMF); IR (mineral oil) 1609, 1043, 1662, 1167 and 1216 cm-1.

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

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

Conditions: temp:154.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 70.0 g (0.5 mol) of 4-fluorobenzoic acid, 30.0 g (0.50 mol) of urea and 0.5 g of phosphorous acid are heated in 100 ml of mesitylene with stirring at from 150 to 158° C. for 8 h. After cooling to 25° C. the solid is filtered off with suction and is washed with 50 ml of mesitylene. The filter cake is introduced into 250 ml of water, and the mixture is adjusted to a pH of 12 with aqueous sodium hydroxide solution and subjected to steam distillation. Subsequently the solid is filtered off with suction and dried at 100° C. 50.7 g of 4-fluorobenzamide are obtained having a melting point of from 147° to 150° C. This corresponds to a yield of 72.9% of theory. By acidification of the aqueous mother liquor to a pH of 2, 5.9 g of 4-fluorobenzoic acid (8.4% of theory) are obtained, which can be employed again in a subsequent batch. After cooling to 25° C. the solid is filtered off with suction is washed with 50 ml of mesitylene The filter cake is introduced into 250 ml of water subjected to steam distillation Subsequently the solid is filtered off with suction dried at 100° C

Conditions: temp:154.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 70.0 g (0.5 mol) of 4-fluorobenzoic acid, 30.0 g (0.50 mol) of urea and 0.5 g of phosphorous acid are heated in 100 ml of mesitylene with stirring at from 150 to 158° C. for 8 h. After cooling to 25° C. the solid is filtered off with suction and is washed with 50 ml of mesitylene. The filter cake is introduced into 250 ml of water, and the mixture is adjusted to a pH of 12 with aqueous sodium hydroxide solution and subjected to steam distillation. Subsequently the solid is filtered off with suction and dried at 100° C. 50.7 g of 4-fluorobenzamide are obtained having a melting point of from 147° to 150° C. This corresponds to a yield of 72.9% of theory. By acidification of the aqueous mother liquor to a pH of 2, 5.9 g of 4-fluorobenzoic acid (8.4% of theory) are obtained, which can be employed again in a subsequent batch. After cooling to 25° C. the solid is filtered off with suction is washed with 50 ml of mesitylene The filter cake is introduced into 250 ml of water subjected to steam distillation Subsequently the solid is filtered off with suction dried at 100° C

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

Procedure: Formula I where R1 is Pyridin-3-yl, R2 is CN, and R3 is 4-Fluorophenyl To a solution of 1 eq. (0.1 g, 0.473 mmol) of 3-(pyridin-3-yloxy)-5-cyano-aniline in 0.47 M in CH2Cl2 (1 mL) and 1.6 eq. of pyridine (0.56 g, 0.71 mmol) was added 3 eq. of 4-fluorobenzoyl chloride (0.225 g, 1.42 mmol) and the resultant mixture stirred at rt overnight. The reaction mixture was diluted with CH2Cl2, washed with sat. NaHCO3, dried (Na2SO4) and concentrated in vacuo. The resultant residue was diluted with toluene and concentrated in vacuo (5 times). Purification by chromatography over silica with 5% MeOH/CH2Cl2 as the eluant afforded 134 mg of a the desired title compound of Formula I, N-[3-cyano-5-(pyridin-3-yloxy)-phenyl]]-4-fluoro-benzamide, as a solid (85% yield). Mpt 169-172° C. MS (M−1) 332.3. washed with sat. NaHCO3 dried (Na2SO4) concentrated in vacuo The resultant residue was diluted with toluene concentrated in vacuo (5 times) Purification by chromatography over silica with 5% MeOH/CH2Cl2 as the eluant