5-FLUORO-2-METHYLBENZYL BROMIDE

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

Procedure: The title compound was prepared in a manner similar to that described in Example 27, Step H from methyl 2-(tert-butoxy)-2-(4-(chroman-6-yl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)acetate and 5-fluoro-2-methylbenzyl bromide. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.51-7.42 (m, 1 H), 7.26-7.21 (m, 1 H), 7.18-7.12 (m, 1 H), 6.98-6.85 (m, 3 H), 6.66 (dt, J=3.3, 9.5 Hz, 1 H), 6.25 (dd, J=3.5, 12.3 Hz, 1 H), 5.62-5.56 (m, 1 H), 5.47-5.34 (m, 2 H), 4.27 (t, J=5.0 Hz, 2 H), 2.94-2.77 (m, 2 H), 2.73-2.66 (m, 3 H), 2.31 (d, J=3.3 Hz, 3 H), 2.14-2.06 (m, 2 H), 1.01-0.91 (s, 9 H); LC/MS (m/z) ES+=517.31 (M+1).

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

Procedure: The title compound is prepared by alkylation of the (RS)-1-(4-hydroxyphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester with 5-fluoro-2-methylbenzyl bromide giving the (RS)-1-[4-(5-fluoro-2-methyl-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methyl ester as a white solid [71% of theory, MS: m/e=358 (M+H)+] which, thereupon, by treatment with methylamine in ethanol at 60° C. during 4 h yields the (RS)-1-[4-(5-fluoro-2-methyl-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide. Yield: 53% of theory as a colorless solid. MS: m/e=357 (M+H)+.

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a N,N-dimethylformamide (1.5 ml) solution of 4-(4-Hydroxy-benzenesulfonyl)-2-methyl-3-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)-piperazine-1-carboxylic acid methylamide (compound of formula XLV, 0.31 g, 0.7 mmol) was added cesium carbonate (0.45 g) and 2-bromomethyl-4-fluoro-1-methyl-benzene (0.214 g, 1.05 mmol). The reaction mixture was stirred at about 45° C. for about 16 hours and then was allowed to cool and was diluted with ethyl acetate and washed with water. The organic layer was dried with sodium sulfate and concentrated in vacuo to give 0.377 g of a compound of formula XLIV. to cool washed with water The organic layer was dried with sodium sulfate concentrated in vacuo

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

Procedure: From the compound of example 16, step 1, (150 mg, 341 μmol) the title compound was prepared analogously as described in example 17, step 1, using 5-fluoro-2-methylbenzyl bromide. Yield: 9 mg.

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

Procedure: According to the method of Example 172, 2-amino-5-chloronicotinamide was reacted with 2-(bromomethyl)-4-fluoro-1-methylbenzene to give the title compound.

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

Procedure: The title compound is prepared by alkylation of the (RS)-1-(4-hydroxyphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester with 5-fluoro-2-methylbenzyl bromide giving the (RS)-1-[4-(5-fluoro-2-methyl-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methyl ester as a white solid [71% of theory, MS: m/e=358 (M+H)+] which, thereupon, by treatment with methylamine in ethanol at 60° C. during 4 h yields the (RS)-1-[4-(5-fluoro-2-methyl-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide. Yield: 53% of theory as a colorless solid. MS: m/e=357 (M+H)+.