(2S)-2-propan-2-ylpiperazine

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

Procedure: A solution of tert-butyl (2S)-2-propan-2-ylpiperazine-1-carboxylate (2 g, 8.76 mmol) in a mixture of ethyl acetate (20 mL) and methanol (20.00 mL) was stirred at room temperature with 4M HCl in dioxane (30 mL) for 40 h under nitrogen. The reaction mixture was evaporated to dryness. The crude product was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 3.5M NH3/MeOH and pure fractions were evaporated to dryness to afford (2S)-2-propan-2-ylpiperazine (1.052 g, 94%) as a white solid. The reaction mixture was evaporated to dryness The crude product was purified by ion exchange chromatography The desired product was eluted from the column were evaporated to dryness

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

Procedure: 341 mg (2.66 mmol) 2-(S)-Isopropyl-piperazine (84) and 657 mg (2.67 mmol, 1.00 eq.) BOC-ON© (2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile) were dissolved in 20 ml 1,4-dioxane and 20 ml water. After adding 2.04 ml (14.64 mmol, 5.50 eq.) triethylamine the solution was stirred at r.t. for 24 h. Then the mixture was added to water and extracted with EtOAc. The comb. org. fractions were washed with brine, dried over Na2SO4 and evaporated. Column chromatography (CH2Cl2/MeOH (3+1)) yielded 454.9 mg (1.99 mmol, 74.90%) 3-(S)-Isopropyl-piperazine-1-carboxylic acid tert-butyl ester (85) as a clear oil. extracted with EtOAc fractions were washed with brine dried over Na2SO4 evaporated

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

Procedure: 341 mg (2.66 mmol) 2-(S)-Isopropyl-piperazine (84) and 657 mg (2.67 mmol, 1.00 eq.) BOC-ON© (2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile) were dissolved in 20 ml 1,4-dioxane and 20 ml water. After adding 2.04 ml (14.64 mmol, 5.50 eq.) triethylamine the solution was stirred at r.t. for 24 h. Then the mixture was added to water and extracted with EtOAc. The comb. org. fractions were washed with brine, dried over Na2SO4 and evaporated. Column chromatography (CH2Cl2/MeOH (3+1)) yielded 454.9 mg (1.99 mmol, 74.90%) 3-(S)-Isopropyl-piperazine-1-carboxylic acid tert-butyl ester (85) as a clear oil. extracted with EtOAc fractions were washed with brine dried over Na2SO4 evaporated

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

Procedure: 341 mg (2.66 mmol) 2-(S)-Isopropyl-piperazine (84) and 657 mg (2.67 mmol, 1.00 eq.) BOC-ON© (2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile) were dissolved in 20 ml 1,4-dioxane and 20 ml water. After adding 2.04 ml (14.64 mmol, 5.50 eq.) triethylamine the solution was stirred at r.t. for 24 h. Then the mixture was added to water and extracted with EtOAc. The comb. org. fractions were washed with brine, dried over Na2SO4 and evaporated. Column chromatography (CH2Cl2/MeOH (3+1)) yielded 454.9 mg (1.99 mmol, 74.90%) 3-(S)-Isopropyl-piperazine-1-carboxylic acid tert-butyl ester (85) as a clear oil. extracted with EtOAc fractions were washed with brine dried over Na2SO4 evaporated

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

Procedure: A solution of tert-butyl (2S)-2-propan-2-ylpiperazine-1-carboxylate (2 g, 8.76 mmol) in a mixture of ethyl acetate (20 mL) and methanol (20.00 mL) was stirred at room temperature with 4M HCl in dioxane (30 mL) for 40 h under nitrogen. The reaction mixture was evaporated to dryness. The crude product was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 3.5M NH3/MeOH and pure fractions were evaporated to dryness to afford (2S)-2-propan-2-ylpiperazine (1.052 g, 94%) as a white solid. The reaction mixture was evaporated to dryness The crude product was purified by ion exchange chromatography The desired product was eluted from the column were evaporated to dryness

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

Procedure: 341 mg (2.66 mmol) 2-(S)-Isopropyl-piperazine (84) and 657 mg (2.67 mmol, 1.00 eq.) BOC-ON© (2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile) were dissolved in 20 ml 1,4-dioxane and 20 ml water. After adding 2.04 ml (14.64 mmol, 5.50 eq.) triethylamine the solution was stirred at r.t. for 24 h. Then the mixture was added to water and extracted with EtOAc. The comb. org. fractions were washed with brine, dried over Na2SO4 and evaporated. Column chromatography (CH2Cl2/MeOH (3+1)) yielded 454.9 mg (1.99 mmol, 74.90%) 3-(S)-Isopropyl-piperazine-1-carboxylic acid tert-butyl ester (85) as a clear oil. extracted with EtOAc fractions were washed with brine dried over Na2SO4 evaporated

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

Procedure: A solution of tert-butyl (2S)-2-propan-2-ylpiperazine-1-carboxylate (2 g, 8.76 mmol) in a mixture of ethyl acetate (20 mL) and methanol (20.00 mL) was stirred at room temperature with 4M HCl in dioxane (30 mL) for 40 h under nitrogen. The reaction mixture was evaporated to dryness. The crude product was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 3.5M NH3/MeOH and pure fractions were evaporated to dryness to afford (2S)-2-propan-2-ylpiperazine (1.052 g, 94%) as a white solid. The reaction mixture was evaporated to dryness The crude product was purified by ion exchange chromatography The desired product was eluted from the column were evaporated to dryness

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (3S)-1-(Benzyl)-3-isopropylpiperazine (358 mg) was dissolved in acetic acid (10 mL), and to the solution 10% palladium on carbon (40 mg) was added, and the mixture was then stirred at 50° C. under a hydrogen atmosphere for 4 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform:ammonia-saturated methanol=20:1) to obtain the title compound. The reaction mixture was filtered the filtrate was concentrated under reduced pressure The residue was purified by column chromatography on silica gel (chloroform:ammonia-saturated methanol=20:1)

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

Procedure: A solution of tert-butyl (2S)-2-propan-2-ylpiperazine-1-carboxylate (2 g, 8.76 mmol) in a mixture of ethyl acetate (20 mL) and methanol (20.00 mL) was stirred at room temperature with 4M HCl in dioxane (30 mL) for 40 h under nitrogen. The reaction mixture was evaporated to dryness. The crude product was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 3.5M NH3/MeOH and pure fractions were evaporated to dryness to afford (2S)-2-propan-2-ylpiperazine (1.052 g, 94%) as a white solid. The reaction mixture was evaporated to dryness The crude product was purified by ion exchange chromatography The desired product was eluted from the column were evaporated to dryness

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

Procedure: To a solution of (S)-3-isopropylpiperazine-2,5-dione (100 mg, 0.6 mmol) in anhydrous THF was added lithium aluminum hydride 1M in THF (1.2 ml, 1.2 mmol). The reaction refluxed for 1 hr, cooled to room temperature, quenched with H2O, filtered, then concentrated under vacuum to yield (S)-2-isopropylpiperazine. This material was combined with 4-chloro-5-methyl-7H-pyrrolo[2,3-d]pyrimidine (85.5 mg, 0.5 mmol) in triethylamine (1 ml) and isopropanol (2 ml). The reaction was heated in a microwave at 180° C. for 30 min, concentrated under vacuum, dissolved in EtOAc, washed with H2O, and concentrated under vacuum to afford (S)-4-(3-isopropylpiperazin-1-yl)-5-methyl-7H-pyrrolo[2,3-d]pyrimidine, carried on without further purification. The reaction refluxed for 1 hr quenched with H2O filtered concentrated under vacuum

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

Procedure: A solution of tert-butyl (2S)-2-propan-2-ylpiperazine-1-carboxylate (2 g, 8.76 mmol) in a mixture of ethyl acetate (20 mL) and methanol (20.00 mL) was stirred at room temperature with 4M HCl in dioxane (30 mL) for 40 h under nitrogen. The reaction mixture was evaporated to dryness. The crude product was purified by ion exchange chromatography, using a SCX column. The desired product was eluted from the column using 3.5M NH3/MeOH and pure fractions were evaporated to dryness to afford (2S)-2-propan-2-ylpiperazine (1.052 g, 94%) as a white solid. The reaction mixture was evaporated to dryness The crude product was purified by ion exchange chromatography The desired product was eluted from the column were evaporated to dryness

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

Procedure: 341 mg (2.66 mmol) 2-(S)-Isopropyl-piperazine (84) and 657 mg (2.67 mmol, 1.00 eq.) BOC-ON© (2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile) were dissolved in 20 ml 1,4-dioxane and 20 ml water. After adding 2.04 ml (14.64 mmol, 5.50 eq.) triethylamine the solution was stirred at r.t. for 24 h. Then the mixture was added to water and extracted with EtOAc. The comb. org. fractions were washed with brine, dried over Na2SO4 and evaporated. Column chromatography (CH2Cl2/MeOH (3+1)) yielded 454.9 mg (1.99 mmol, 74.90%) 3-(S)-Isopropyl-piperazine-1-carboxylic acid tert-butyl ester (85) as a clear oil. extracted with EtOAc fractions were washed with brine dried over Na2SO4 evaporated