3-fluoro-5-(hydroxymethyl)benzonitrile

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

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

Procedure: The title compound or its salt was prepared by a procedure similar to that described for E2 starting from 3-fluoro-5-(hydroxymethyl)benzonitrile and 8-chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one.

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

Procedure: The title compound was prepared by a procedure similar to that described for E9 starting from 3-fluoro-5-(hydroxymethyl)benzonitrile and 7-chloro-1,2-dimethyl-2,3-dihydroi-midazo[1,2-c]pyrimidin-5(1H)-one.

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

Procedure: The title compound was prepared by a procedure similar to that described for E1 starting from 3-fluoro-5-(hydroxymethyl)benzonitrile and (S)-tert-butyl 7-chloro-2-methyl-5-oxo-2,3-dihydroimidazo[1,2-c]pyrimidine-1(5H)-carboxylate.

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

Procedure: (Step 3) Triphenylphosphine (1.91 g) was suspended in acetonitrile (50 ml), bromine (0.38 ml) was added, and the suspension was stirred for 30 min. 3-Fluoro-5-(hydroxymethyl)benzonitrile (1.1 g) synthesized by the method of Steps 1 and 2 was added to the reaction mixture, and the mixture was stirred at 85° C. for 2 hr. The reaction solution was quenched with water and extracted with ethyl acetate. The extract was washed with aqueous sodium hydrogen carbonate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was treated by basic silica gel chromatography (ethyl acetate:hexane=1:5) to give 3-(bromomethyl)-5-fluorobenzonitrile (0.69 g). was added to the reaction mixture the mixture was stirred at 85° C. for 2 hr The reaction solution was quenched with water extracted with ethyl acetate The extract was washed with aqueous sodium hydrogen carbonate solution with saturated brine, and dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure the obtained residue was treated by basic silica gel chromatography (ethyl acetate:hexane=1:5)

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (Step 2) To a mixed solution of methyl 3-cyano-5-fluorobenzoate (0.55 g) obtained in Step 1 in tetrahydrofuran:ethanol=10:1 (22 ml) was added lithium tetrahydroborate (0.10 g) at 0° C. After stirring at 55° C. for 1 hr, the reaction solution was quenched with ice and extracted with ethyl acetate. The extract was washed with 1N hydrochloric acid and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give 3-fluoro-5-(hydroxymethyl)benzonitrile (0.29 g). the reaction solution was quenched with ice extracted with ethyl acetate The extract was washed with 1N hydrochloric acid with saturated brine, and dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure

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

Procedure: The title compound or its salt was prepared by a procedure similar to that described for E2 starting from 3-fluoro-5-(hydroxymethyl)benzonitrile and 8-chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one.