3-(aminomethyl)cyclohexan-1-ol

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

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-ethyl-6-nitro-4-chloro-1H-pyrazolo[3,4-b]quinoline (2.7 g, 17.8 mmol), triethylamine (3 mL, 0.02 mol), DMSO (15 mL) and 3-hydroxycyclohexylmethylamine (4.97 g, 18 mmol) was heated at 110° C. overnight. The reaction mixture was poured into ice-water (200 mL)/NH4OH (10 mL) and the solid which formed was collected by filtration. The filtrate was then extracted with CH2Cl2 (2×100 mL). The solid was stirred and sonicated with CH2Cl2 (2×200 mL) and any solids which did not go into solution were collected by filtration. All of the above CH2Cl2 filtrates and extracts were combined, washed with water and evaporated. The residue was slurried with ethyl acetate (10-15 mL)/ether (20 mL) and a red colored solid was collected by filtration and washed with ether. The solid was purified by column chromatography (2×) on silica gel (note that the solid was preloaded onto 50-100 g of silica gel) eluting with 40% THF/cyclohexane and each of the diastereomers which was isolated was dissolved in hot THF, filtered and the solvent was evaporated. Each of the residues was slurried with ethanol (5 mL), filtered and dried to afford 0.69 g of 1-ethyl-6-nitro-N-(3-hydroxycyclohexylmethyl)-1 H-pyrazolo[3,4-b]quinolin-4-amine (the RS,SR diastereomer which is labelled as Example 36(a)), m.p. 236°-238° C. and 2.23 g of 1-ethyl-6-nitro-N-(3-hydroxycyclohexylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amine (the RR,SS diastereomer which is labelled as Example 36(b)), m.p. 247°-248° C. the solid which formed was collected by filtration The filtrate was then extracted with CH2Cl2 (2×100 mL) sonicated with CH2Cl2 (2×200 mL) were collected by filtration washed with water evaporated a red colored solid was collected by filtration washed with ether The solid was purified by column chromatography (2×) on silica gel (note that the solid eluting with 40% THF/cyclohexane each of the diastereomers which was isolated filtered the solvent was evaporated filtered dried

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

Procedure: 37.2 g of 3-(nitromethyl)cyclohexanone are reduced with lithium aluminum hydride in analogy to the procedure for Example 2. In this way 7.5 g (24.5% of theory) of viscous oily 3-(aminomethyl)cyclohexanol are obtained.

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

Procedure: 37.2 g of 3-(nitromethyl)cyclohexanone are reduced with lithium aluminum hydride in analogy to the procedure for Example 2. In this way 7.5 g (24.5% of theory) of viscous oily 3-(aminomethyl)cyclohexanol are obtained.

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

Procedure: 37.2 g of 3-(nitromethyl)cyclohexanone are reduced with lithium aluminum hydride in analogy to the procedure for Example 2. In this way 7.5 g (24.5% of theory) of viscous oily 3-(aminomethyl)cyclohexanol are obtained.

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-ethyl-6-nitro-4-chloro-1H-pyrazolo[3,4-b]quinoline (2.7 g, 17.8 mmol), triethylamine (3 mL, 0.02 mol), DMSO (15 mL) and 3-hydroxycyclohexylmethylamine (4.97 g, 18 mmol) was heated at 110° C. overnight. The reaction mixture was poured into ice-water (200 mL)/NH4OH (10 mL) and the solid which formed was collected by filtration. The filtrate was then extracted with CH2Cl2 (2×100 mL). The solid was stirred and sonicated with CH2Cl2 (2×200 mL) and any solids which did not go into solution were collected by filtration. All of the above CH2Cl2 filtrates and extracts were combined, washed with water and evaporated. The residue was slurried with ethyl acetate (10-15 mL)/ether (20 mL) and a red colored solid was collected by filtration and washed with ether. The solid was purified by column chromatography (2×) on silica gel (note that the solid was preloaded onto 50-100 g of silica gel) eluting with 40% THF/cyclohexane and each of the diastereomers which was isolated was dissolved in hot THF, filtered and the solvent was evaporated. Each of the residues was slurried with ethanol (5 mL), filtered and dried to afford 0.69 g of 1-ethyl-6-nitro-N-(3-hydroxycyclohexylmethyl)-1 H-pyrazolo[3,4-b]quinolin-4-amine (the RS,SR diastereomer which is labelled as Example 36(a)), m.p. 236°-238° C. and 2.23 g of 1-ethyl-6-nitro-N-(3-hydroxycyclohexylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amine (the RR,SS diastereomer which is labelled as Example 36(b)), m.p. 247°-248° C. the solid which formed was collected by filtration The filtrate was then extracted with CH2Cl2 (2×100 mL) sonicated with CH2Cl2 (2×200 mL) were collected by filtration washed with water evaporated a red colored solid was collected by filtration washed with ether The solid was purified by column chromatography (2×) on silica gel (note that the solid eluting with 40% THF/cyclohexane each of the diastereomers which was isolated filtered the solvent was evaporated filtered dried

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-ethyl-6-nitro-4-chloro-1H-pyrazolo[3,4-b]quinoline (2.7 g, 17.8 mmol), triethylamine (3 mL, 0.02 mol), DMSO (15 mL) and 3-hydroxycyclohexylmethylamine (4.97 g, 18 mmol) was heated at 110° C. overnight. The reaction mixture was poured into ice-water (200 mL)/NH4OH (10 mL) and the solid which formed was collected by filtration. The filtrate was then extracted with CH2Cl2 (2×100 mL). The solid was stirred and sonicated with CH2Cl2 (2×200 mL) and any solids which did not go into solution were collected by filtration. All of the above CH2Cl2 filtrates and extracts were combined, washed with water and evaporated. The residue was slurried with ethyl acetate (10-15 mL)/ether (20 mL) and a red colored solid was collected by filtration and washed with ether. The solid was purified by column chromatography (2×) on silica gel (note that the solid was preloaded onto 50-100 g of silica gel) eluting with 40% THF/cyclohexane and each of the diastereomers which was isolated was dissolved in hot THF, filtered and the solvent was evaporated. Each of the residues was slurried with ethanol (5 mL), filtered and dried to afford 0.69 g of 1-ethyl-6-nitro-N-(3-hydroxycyclohexylmethyl)-1 H-pyrazolo[3,4-b]quinolin-4-amine (the RS,SR diastereomer which is labelled as Example 36(a)), m.p. 236°-238° C. and 2.23 g of 1-ethyl-6-nitro-N-(3-hydroxycyclohexylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amine (the RR,SS diastereomer which is labelled as Example 36(b)), m.p. 247°-248° C. the solid which formed was collected by filtration The filtrate was then extracted with CH2Cl2 (2×100 mL) sonicated with CH2Cl2 (2×200 mL) were collected by filtration washed with water evaporated a red colored solid was collected by filtration washed with ether The solid was purified by column chromatography (2×) on silica gel (note that the solid eluting with 40% THF/cyclohexane each of the diastereomers which was isolated filtered the solvent was evaporated filtered dried

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

Procedure: 37.2 g of 3-(nitromethyl)cyclohexanone are reduced with lithium aluminum hydride in analog to the procedure for Example 2. In this way 7.5 g (24.5% of theory) of viscous oily 3-(aminomethyl)cyclohexanol are obtained. Rf =0.04 CH2Cl2 :CH3OH=9:1

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: and (b) A mixture of 1-ethyl-6-nitro-4-chloro-1H-pyrazolo[3,4-b]quinoline (2.7 g, 17.8 mmol), triethylamine (3 ml, 0.02 mol), DMSO (15 ml) and 3-hydroxycyclohexylmethylamine (4.97 g, 18 mmol) is heated at 110° C. overnight. The reaction mixture is poured into ice water (200 ml)/NH4OH (10 ml) and the solid which forms is collected by filtration. The filtrate is then extracted with CH2Cl2 (2×100 ml). The solid is stirred and sonicated with CH2Cl2 (2×200 ml), and any solids which did not go into solution are collected by filtration. All of the above CH2Cl2 filtrates and extracts are combined, washed with water and evaporated. The residue is slurried with ethyl acetate (10-15 ml)/ether (20 ml) and a red colored solid is collected by filtration and washed with ether. The solid is purified by column chromatography (2×) on silica gel (note that the solid is preloaded onto 50-100 g of silica gel) eluting with 40% THF/cyclohexane and each of the diastereomers which is isolated is dissolved in hot THF, filtered and the solvent is evaporated. Each of the residues is slurried with ethanol (5 ml), filtered and dried to afford 0.69 g of 1-ethyl-6-nitro-N-(3-hydroxycyclohexylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amine (the RS,SR diastereomer which is labelled as Example 36(a)), m.p. 236°-238° C. and 2.23 g of 1-ethyl-6-nitro-N-(3-hydroxycyclohexylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amine (the RR,SS diastereomer which is labelled as Example 36(b)), m.p. 247°-248° C. the solid which forms is collected by filtration The filtrate is then extracted with CH2Cl2 (2×100 ml) sonicated with CH2Cl2 (2×200 ml) are collected by filtration washed with water evaporated a red colored solid is collected by filtration washed with ether The solid is purified by column chromatography (2×) on silica gel (note that the solid eluting with 40% THF/cyclohexane each of the diastereomers which is isolated filtered the solvent is evaporated filtered dried

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

Procedure: 37.2 g of 3-(nitromethyl)cyclohexanone are reduced with lithium aluminum hydride in analogy to the procedure for Example 2. In this way 7.5 g (24.5% of theory) of viscous oily 3-(aminomethyl)cyclohexanol are obtained.

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

Procedure: 37.2 g of 3-(nitromethyl)cyclohexanone are reduced with lithium aluminum hydride in analogy to the procedure for Example 2. In this way 7.5 g (24.5% of theory) of viscous oily 3-(aminomethyl)cyclohexanol are obtained.

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

Procedure: 37.2 g of 3-(nitromethyl)cyclohexanone are reduced with lithium aluminum hydride in analogy to the procedure for Example 2. In this way 7.5 g (24.5% of theory) of viscous oily 3-(aminomethyl)cyclohexanol are obtained.