4-amino-2-methylbutan-1-ol

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

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

Procedure: 2-Nitrobenzaldehyde (7.33 g, 48.5 mmol) and 4-amino-2-methylbutanol (5.00 g, 48.5 mmol) were dissolved in toluene (50 ml) and heated to reflux for two hours with Dean Stark dehydration apparatus. After allowed to cool, the solvent was evaporated under reduced pressure. The obtained concentrate was dissolved in methanol (100 ml), added with sodium borohydride (2.75 g, 72.8 mmol) under ice cooled condition and stirred at the same temperature for two hours. The reaction mixture was further stirred at room temperature for two hours, adjusted to pH 4 by adding 1N hydrochloric acid, and the solvent was evaporated under reduced pressure. Water (30 ml) was added to dissolve the concentrate and after extracted with ethyl acetate, pH was adjusted to 8 by added a saturated sodium hydrogen carbonate aqueous solution and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure to obtain 2-methyl-4-(2-nitrobenzylamino)butanol (11.12 g). heated to reflux for two hours with Dean Stark dehydration apparatus to cool the solvent was evaporated under reduced pressure The obtained concentrate was dissolved in methanol (100 ml) The reaction mixture was further stirred at room temperature for two hours the solvent was evaporated under reduced pressure Water (30 ml) was added to dissolve the concentrate after extracted with ethyl acetate, pH by added a saturated sodium hydrogen carbonate aqueous solution extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure

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

Procedure: 2-Nitrobenzaldehyde (7.33 g, 48.5 mmol) and 4-amino-2-methylbutanol (5.00 g, 48.5 mmol) were dissolved in toluene (50 ml) and heated to reflux for two hours with Dean Stark dehydration apparatus. After allowed to cool, the solvent was evaporated under reduced pressure. The obtained concentrate was dissolved in methanol (100 ml), added with sodium borohydride (2.75 g, 72.8 mmol) under ice cooled condition and stirred at the same temperature for two hours. The reaction mixture was further stirred at room temperature for two hours, adjusted to pH 4 by adding 1N hydrochloric acid, and the solvent was evaporated under reduced pressure. Water (30 ml) was added to dissolve the concentrate and after extracted with ethyl acetate, pH was adjusted to 8 by added a saturated sodium hydrogen carbonate aqueous solution and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure to obtain 2-methyl-4-(2-nitrobenzylamino)butanol (11.12 g). heated to reflux for two hours with Dean Stark dehydration apparatus to cool the solvent was evaporated under reduced pressure The obtained concentrate was dissolved in methanol (100 ml) The reaction mixture was further stirred at room temperature for two hours the solvent was evaporated under reduced pressure Water (30 ml) was added to dissolve the concentrate after extracted with ethyl acetate, pH by added a saturated sodium hydrogen carbonate aqueous solution extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure

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

Procedure: The process is carried out as in stage 2 of Example 3, but using 300 mg of 2-fluoro-4-[4-(quinolin-3-yl)-9H-carbazol-9-yl]benzonitrile, obtained according to stage 1 of Example 32, 301 mg of potassium carbonate and 1.50 g of 4-amino-2(R,S)-methylbutanol in 3 ml of dimethyl sulphoxide. 1.38 ml of a 1M aqueous solution of sodium hydroxide, 1.336 ml of a 30% aqueous solution of hydrogen peroxide and 7 ml of ethanol are then added to the reaction medium. After treatment as in stage 3 of Example 3, and then purification by flash chromatography on silica gel, elution being carried out with a mixture of dichloromethane and ethanol (95/5 by volume), followed by crystallization from 5 ml of ethyl acetate, 225 mg of 4-[4-(quinolin-3-yl)-9H-carbazol-9-yl]-2-(4-hydroxy-3(R,S)-methylbutylamino)benzamide are thus obtained in the form of a beige solid, the characteristics of which are the following: obtained After treatment as in stage 3 of Example 3, and then purification by flash chromatography on silica gel, elution being carried out with a mixture of dichloromethane and ethanol (95/5 by volume) followed by crystallization from 5 ml of ethyl acetate, 225 mg of 4-[4-(quinolin-3-yl)-9H-carbazol-9-yl]-2-(4-hydroxy-3(R,S)-methylbutylamino)benzamide are thus obtained in the form of a beige solid

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

Procedure: To a solution of compound (7) (540 mg, 2 mmol, Preparation 2) and 4-amino-2-methyl-butan-1-ol (230 mg, 2 mmol) in DMSO (20 mL) was added Et3N (404 mg, 4 mmol). The reaction mixture was stirred at 110° C. overnight. The reaction mixture was diluted with water, extracted with EtOAc (50 mL×3). The combined organic extracts were washed with water (30 mL) and brine (30 mL), dried over Na2SO4 and filtered. The filtrate was evaporated in vacuo and the residue was purified by flash column chromatography (EtOAc: Petrol ether=3:1) on silica gel to give (36). (557 mg, 1.6 mmol, yield 80%). extracted with EtOAc (50 mL×3) The combined organic extracts were washed with water (30 mL) and brine (30 mL) dried over Na2SO4 filtered The filtrate was evaporated in vacuo the residue was purified by flash column chromatography (EtOAc: Petrol ether=3:1) on silica gel

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

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

Procedure: 2-Nitrobenzaldehyde (7.33 g, 48.5 mmol) and 4-amino-2-methylbutanol (5.00 g, 48.5 mmol) were dissolved in toluene (50 ml) and heated to reflux for two hours with Dean Stark dehydration apparatus. After allowed to cool, the solvent was evaporated under reduced pressure. The obtained concentrate was dissolved in methanol (100 ml), added with sodium borohydride (2.75 g, 72.8 mmol) under ice cooled condition and stirred at the same temperature for two hours. The reaction mixture was further stirred at room temperature for two hours, adjusted to pH 4 by adding 1N hydrochloric acid, and the solvent was evaporated under reduced pressure. Water (30 ml) was added to dissolve the concentrate and after extracted with ethyl acetate, pH was adjusted to 8 by added a saturated sodium hydrogen carbonate aqueous solution and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure to obtain 2-methyl-4-(2-nitrobenzylamino)butanol (11.12 g). heated to reflux for two hours with Dean Stark dehydration apparatus to cool the solvent was evaporated under reduced pressure The obtained concentrate was dissolved in methanol (100 ml) The reaction mixture was further stirred at room temperature for two hours the solvent was evaporated under reduced pressure Water (30 ml) was added to dissolve the concentrate after extracted with ethyl acetate, pH by added a saturated sodium hydrogen carbonate aqueous solution extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure