1-(aminomethyl)-N,N-dimethylcyclohexan-1-amine

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-{[2-(isopropylsulfonyl)phenyl]amino}-2-(methylsulfanyl)-6-oxo-1,6-dihydropyrimidine-5-carboxamide (Preparation Example 294) (200 mg), 1-(aminomethyl)-N,N-dimethylcyclohexylamine (409 mg) and NMP (1 mL) was heated at 180° C. for 10 minutes using a microwave reaction system. After cooling, the reaction liquid was diluted with ethyl acetate, and the precipitated crystal was collected by filtration and washed with ethyl acetate to give a white solid. To the white solid, a mixed solvent of ethanol and water was added, heated and then cooled, and the precipitated solid was collected by filtration to give 2-({[1-(dimethylamino)cyclohexyl]methyl}amino)-4-{[2-(isopropylsulfonyl)phenyl]amino}-6-oxo-1,6-dihydropyrimidine-5-carboxamide (136 mg) as a white solid. a microwave reaction system After cooling the reaction liquid the precipitated crystal was collected by filtration washed with ethyl acetate to give a white solid heated cooled the precipitated solid was collected by filtration

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-{[2-(isopropylsulfonyl)phenyl]amino}-2-(methylsulfanyl)-6-oxo-1,6-dihydropyrimidine-5-carboxamide (Preparation Example 294) (200 mg), 1-(aminomethyl)-N,N-dimethylcyclohexylamine (409 mg) and NMP (1 mL) was heated at 180° C. for 10 minutes using a microwave reaction system. After cooling, the reaction liquid was diluted with ethyl acetate, and the precipitated crystal was collected by filtration and washed with ethyl acetate to give a white solid. To the white solid, a mixed solvent of ethanol and water was added, heated and then cooled, and the precipitated solid was collected by filtration to give 2-({[1-(dimethylamino)cyclohexyl]methyl}amino)-4-{[2-(isopropylsulfonyl)phenyl]amino}-6-oxo-1,6-dihydropyrimidine-5-carboxamide (136 mg) as a white solid. a microwave reaction system After cooling the reaction liquid the precipitated crystal was collected by filtration washed with ethyl acetate to give a white solid heated cooled the precipitated solid was collected by filtration

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

Procedure: A solution of p-toluoyl chloride (1 g.) 1-aminomethylcyclohexyl dimethylamine (1 g.) and triethylamine (0.65 g.) in benzene (60 ml.) was heated under reflux for 1.5 hrs. The excess benzene was evaporated under reduced pressure, the residue dissolved in water and extracted with chloroform. The extracts were dried (anhyd. sodium sulphate) and the chloroform evaporated under reduced pressure to give an oil which solidified on cooling. Excess ethereal hydrochloric acid was added to an ethereal solution of the solid and the excess ether removed under reduced pressure. The solid residue was crystallised from isopropanol/petroleum ether (80-100) to give 4-methylbenzamido methyl cyclohexyl dimethylamine hydrochloride m.p. 199°-201° (0.7 g.). under reflux for 1.5 hrs The excess benzene was evaporated under reduced pressure the residue dissolved in water extracted with chloroform The extracts were dried (anhyd. sodium sulphate) the chloroform evaporated under reduced pressure to give an oil which on cooling the excess ether removed under reduced pressure The solid residue was crystallised from isopropanol/petroleum ether (80-100)

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

Procedure: A mixture of 1-aminomethylcyclohexyldimethylamine (1.0 g), 4-fluorobenzoyl chloride (2 ml) and pyridine (10 ml) was allowed to stand at room temperature for 1 hr. The crystalline material produced was filtered and recrystallised several times from ethanol/ether to give colourless needles of 1-(4-fluorobenzamidomethyl)-cyclohexyl dimethylamine hydrochloride m.p. 238°-239°. The crystalline material produced was filtered recrystallised several times from ethanol/ether

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

Procedure: A mixture of 1-aminomethylcyclohexyldimethylamine (1.5 g), benzoyl chloride (3 ml) and pyridine (10 ml) was allowed to stand at room temperature for 1 hr. The crystalline mass was filtered and recrystallised several times from 95% ethanol to give colourless prisms of 1-benzamidomethylcyclohexyldimethylamine hydrochloride m.p. 245°-6°. The crystalline mass was filtered recrystallised several times from 95% ethanol

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

Procedure: A mixture of 1-aminomethylcyclohexyl dimethylamine (1.0 g.), 3,4-dichlorobenzoyl chloride (2 ml) and pyridine (10 ml) was allowed to stand at room temp. for 1 hr. The pale yellow solid produced was filtered and recrystallised from ethanol/ether to give colourless microneedles of 1-(3,4-dichlorobenzamidomethyl)-cyclohexyldimethylamine hydrochloride m.p. 215°-16°. The pale yellow solid produced was filtered recrystallised from ethanol/ether

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

Procedure: A solution of p-toluoyl chloride (1 g.) 1-aminomethylcyclohexyl dimethylamine (1 g.) and triethylamine (0.65 g.) in benzene (60 ml.) was heated under reflux for 1.5 hrs. The excess benzene was evaporated under reduced pressure, the residue dissolved in water and extracted with chloroform. The extracts were dried (anhyd. sodium sulphate) and the chloroform evaporated under reduced pressure to give an oil which solidified on cooling. Excess ethereal hydrochloric acid was added to an ethereal solution of the solid and the excess ether removed under reduced pressure. The solid residue was crystallised from isopropanol/petroleum ether (80-100) to give 4-methylbenzamido methyl cyclohexyl dimethylamine hydrochloride m.p. 199°-201° (0.7 g.). under reflux for 1.5 hrs The excess benzene was evaporated under reduced pressure the residue dissolved in water extracted with chloroform The extracts were dried (anhyd. sodium sulphate) the chloroform evaporated under reduced pressure to give an oil which on cooling the excess ether removed under reduced pressure The solid residue was crystallised from isopropanol/petroleum ether (80-100)

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

Procedure: A mixture of 1-aminomethylcyclohexyldimethylamine (1.0 g), 4-fluorobenzoyl chloride (2 ml) and pyridine (10 ml) was allowed to stand at room temperature for 1 hr. The crystalline material produced was filtered and recrystallised several times from ethanol/ether to give colourless needles of 1-(4-fluorobenzamidomethyl)-cyclohexyl dimethylamine hydrochloride m.p. 238°-239° . The crystalline material produced was filtered recrystallised several times from ethanol/ether

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

Procedure: A mixture of 1-aminomethylcyclohexyldimethylamine (1.5 g), benzoyl chloride (3 ml) and pyridine (10 ml) was allowed to stand at room temperature for 1 hr. The crystalline mass was filtered and recrystallised several times from 95% ethanol to give colourless prisms of 1-benzamidomethylcyclohexyldimethylamine hydrochloride m.p. 245°-6° . The crystalline mass was filtered recrystallised several times from 95% ethanol

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

Procedure: A mixture of 1-aminomethylcyclohexyl dimethylamine (1.0 g.), 3,4-dichlorobenzoyl chloride (2 ml) and pyridine (10 ml) was allowed to stand at room temp. for 1 hr. The pale yellow solid produced was filtered and recrystallised from ethanol/ether to give a colourless microneedles of 1-(3,4-dichlorobenzamidomethyl)-cyclohexyldimethylamine hydrochloride m.p. 215°-16° . The pale yellow solid produced was filtered recrystallised from ethanol/ether

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

Procedure: Synthesised from 1-(dimethylaminocyclohexyl)methylamine and 4-butyloxy benzoyl chloride following the procedure of Example 1 (g and purified by LCMS to obtain the product as a trifluoroacetate salt. 1H NMR (CDCl3) δ: 0.97 (t, 3H, J=4 Hz), 1.18 (m, 1H), 1.49 (m, 2H), 1.67 (m, 4H), 1.80 (m, 5H), 2.01 (d, 2H, J=3 Hz), 2.79 (s, 6H), 4.01 (m, 4H), 6.93 (d, 2H, J=4 Hz), 8.18 (d, 2H, J=4 Hz), 8.47 (m, 1H), 11.90 (s, 1H). LCMS m/z 333.2 (MH+; 96.5%). HRMS (FAB) calc. 333.2539, found 333.2536. purified by LCMS

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-{[2-(isopropylsulfonyl)phenyl]amino}-2-(methylsulfanyl)-6-oxo-1,6-dihydropyrimidine-5-carboxamide (Preparation Example 294) (200 mg), 1-(aminomethyl)-N,N-dimethylcyclohexylamine (409 mg) and NMP (1 mL) was heated at 180° C. for 10 minutes using a microwave reaction system. After cooling, the reaction liquid was diluted with ethyl acetate, and the precipitated crystal was collected by filtration and washed with ethyl acetate to give a white solid. To the white solid, a mixed solvent of ethanol and water was added, heated and then cooled, and the precipitated solid was collected by filtration to give 2-({[1-(dimethylamino)cyclohexyl]methyl}amino)-4-{[2-(isopropylsulfonyl)phenyl]amino}-6-oxo-1,6-dihydropyrimidine-5-carboxamide (136 mg) as a white solid. a microwave reaction system After cooling the reaction liquid the precipitated crystal was collected by filtration washed with ethyl acetate to give a white solid heated cooled the precipitated solid was collected by filtration