(4-aminocyclohexyl)methanol

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

Procedure: To a solution of (1r,4r)-4-aminocyclohexanecarboxylic acid (860 mg, 6.0 mmol, 1.0 eq) in THF (10 mL) was added dropwise BH3/THF (1.0 mol/L in THF, 30 mL, 5.0 equiv.) at 0° C. The reaction was allowed to warm to room temperature. The reaction was heated at reflux for 48 hours. The reaction was quenched with AcOH and concentrated in vacuo to get crude ((1r,4r)-4-aminocyclohexyl)methanol (600 mg, 78%) which was used to the next step without further purification. MS: m/z 130.1 (M+H)+. The reaction was heated at reflux for 48 hours The reaction was quenched with AcOH concentrated in vacuo

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

Procedure: To a solution of (1r,4r)-4-aminocyclohexanecarboxylic acid (860 mg, 6.0 mmol, 1.0 eq) in THF (10 mL) was added dropwise BH3/THF (1.0 mol/L in THF, 30 mL, 5.0 equiv.) at 0° C. The reaction was allowed to warm to room temperature. The reaction was heated at reflux for 48 hours. The reaction was quenched with AcOH and concentrated in vacuo to get crude ((1r,4r)-4-aminocyclohexyl)methanol (600 mg, 78%) which was used to the next step without further purification. MS: m/z 130.1 (M+H)+. The reaction was heated at reflux for 48 hours The reaction was quenched with AcOH concentrated in vacuo

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

Procedure: To a solution of (1r,4r)-4-aminocyclohexanecarboxylic acid (860 mg, 6.0 mmol, 1.0 eq) in THF (10 mL) was added dropwise BH3/THF (1.0 mol/L in THF, 30 mL, 5.0 equiv.) at 0° C. The reaction was allowed to warm to room temperature. The reaction was heated at reflux for 48 hours. The reaction was quenched with AcOH and concentrated in vacuo to get crude ((1r,4r)-4-aminocyclohexyl)methanol (600 mg, 78%) which was used to the next step without further purification. MS: m/z 130.1 (M+H)+. The reaction was heated at reflux for 48 hours The reaction was quenched with AcOH concentrated in vacuo

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

Procedure: Prepared as in Example 24a from (4-Aminocyclohexyl)methanol and isonicotinic acid as a yellow oil (100%). MS 235 (MH+).

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

Procedure: Prepared as in Example 24a from (4-Aminocyclohexyl)methanol and isonicotinic acid as a yellow oil (100%). MS 235 (MH+).

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

Procedure: Prepared as in Example 24a from (4-Aminocyclohexyl)methanol and isonicotinic acid as a yellow oil (100%). MS 235 (MH+).

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

Procedure: Sulfone 11.1 (350 mg, 104 mmol) was combined with 4-aminocyclohexylmethanol 1:1 cis/trans) (400 mg, 3.3 mmol) (prepared as described in Chem.Ber.; GE; 96; 1963; 2377-2386) with 0.3 mL of 1-methyl-2-pyrrolidinone. The mixture was heated at 1000 for 2 hours at which time it was cooled to room temperature. The reaction mixture was added to water and extracted with ethyl acetate, washed with water, dried, and concentrated in vacuo. The residue was purified by column chromatography on silica gel using 10:90 methanol/dichloromethane as eluant The column fractions containing the product were concentrated to a foam which was resuspended in methanol. Addition of hydrochloric acid (1.0M/Et2O, 1.0 equivalent) gave a salt which was filtered to give the hydrochloride salt of 3-(2-chlorophenyl)-7-(4-hydroxymethylcyclohexylamino)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one. The mixture was heated at 1000 for 2 hours at which time it extracted with ethyl acetate washed with water dried concentrated in vacuo The residue was purified by column chromatography on silica gel using 10:90 methanol/dichloromethane as eluant The column fractions containing the product were concentrated to a foam which gave a salt which was filtered

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

Procedure: To a solution of (1r,4r)-4-aminocyclohexanecarboxylic acid (860 mg, 6.0 mmol, 1.0 eq) in THF (10 mL) was added dropwise BH3/THF (1.0 mol/L in THF, 30 mL, 5.0 equiv.) at 0° C. The reaction was allowed to warm to room temperature. The reaction was heated at reflux for 48 hours. The reaction was quenched with AcOH and concentrated in vacuo to get crude ((1r,4r)-4-aminocyclohexyl)methanol (600 mg, 78%) which was used to the next step without further purification. MS: m/z 130.1 (M+H)+. The reaction was heated at reflux for 48 hours The reaction was quenched with AcOH concentrated in vacuo