tert-butyl N-(3-methyl-1-oxobutan-2-yl)carbamate

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

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

Procedure: To a solution of 1.25 g of tert-butyl 3-methyl-1-oxobutan-2-ylcarbamate (Formula 21) and 1.79 g of dimethyl 1-diazo-2-oxopropylphosphonate (Formula 15) in 80 mL of methanol at 0° C. was added 1.72 g of potassium carbonate. The mixture was stirred at room temperature for 16 hours then quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. Column chromatography (15% ethyl acetate/hexane) gave 1.01 g of tert-butyl 4-methylpent-1-yn-3-ylcarbamate (Formula 22) as a clear oil. 1H NMR (300 MHz, CDCl3) δ 0.98-1.00 (m, 6H), 1.45 (s, 9H), 1.87-1.93 (m, 1H), 2.24-2.25 (m, 1H), 4.32 (br, 1H). then quenched with saturated ammonium chloride solution extracted with ethyl acetate The combined organic layers were washed with brine dried over sodium sulfate concentrated

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

Procedure: To a solution of 1.25 g of tert-butyl 3-methyl-1-oxobutan-2-ylcarbamate (Formula 21) and 1.79 g of dimethyl 1-diazo-2-oxopropylphosphonate (Formula 15) in 80 mL of methanol at 0° C. was added 1.72 g of potassium carbonate. The mixture was stirred at room temperature for 16 hours then quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. Column chromatography (15% ethyl acetate/hexane) gave 1.01 g of tert-butyl 4-methylpent-1-yn-3-ylcarbamate (Formula 22) as a clear oil. 1H NMR (300 MHz, CDCl3) δ 0.98-1.00 (m, 6H), 1.45 (s, 9H), 1.87-1.93 (m, 1H), 2.24-2.25 (m, 1H), 4.32 (br, 1H). then quenched with saturated ammonium chloride solution extracted with ethyl acetate The combined organic layers were washed with brine dried over sodium sulfate concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1.75 g of tert-butyl 1-hydroxy-3-methylbutan-2-ylcarbamate (Formula 20) in 25 mL of DMSO was added 3.6 mL of triethylamine. The solution was cooled to 0° C. and 4.1 grams of sulfur trioxide pyridine complex in 25 mL of DMSO was added. The reaction mixture was stirred at room temperature for 1 hour. Then, the mixture was poured onto ice-water and extracted with ethyl acetate. The organic layers were washed with 10% acetic acid, water, 5% sodium bicarbonate, and brine, dried over sodium sulfate and concentrated. Column chromatography (30% ethyl acetate/hexane) gave 1.25 g of tert-butyl 3-methyl-1-oxobutan-2-ylcarbamate (Formula 21) as a clear oil. 1H NMR (300 MHz, CDCl3) δ 0.95 (d, J=7.32 Hz, 3H), 1.03 (d, J=6.83 Hz, 3H), 1.45 (s, 9H), 2.27-2.29 (m, 1H), 4.24-4.26 (m, 1H), 9.65 (s, 1H). Then, the mixture was poured onto ice-water extracted with ethyl acetate The organic layers were washed with 10% acetic acid, water, 5% sodium bicarbonate, and brine dried over sodium sulfate concentrated

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

Procedure: Method C was followed, using 5-(6-chloro-9H-β-carbolin-8-ylcarbamoyl)-2,2-dimethyl-morpholine-4-carboxylic acid tert-butyl ester and the appropriate aldehyde, (1-formyl-2-methyl-propyl)-carbamic acid tert-butyl ester. 1H-NMR (DMSO-d6, 300 MHz) δ 9.05 (s, 1); 8.37 (d, 1); 8.21 (d, 1); 8.16 (dd, 1); 7.90 (d, 1); 6.71 (br s, 2); 3.93-3.86 (m, 2); 3.18-3.14 (m, 1); 2.91 (d, 1); 2.70-2.65 (m, 2); 2.21 (dd, 1); 2.15 (d, 1); 1.74-1.66 (m, 1); 1.31 (s, 3); 1.19 (s, 3); 0.85 (d, 3); 0.80 (d, 3). NH4OAc standard conditions. DAD Rf=1.27 min. M+H=444.

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

Procedure: To a solution of Dess-Martin periodinane (3.12 g, 0.0073 mol, 1.5 eq) in dichloromethane (25 mL) was added a solution of N-Boc-L-valinol (1 g, 0.0049 mol, 1 eq) in dichloromethane (25 mL). The reaction mixture was stirred at room temperature for 3 h and was diluted with diethyl ether (50 mL). The mixture was poured into an aqueous saturated solution of sodium bicarbonate (100 mL) containing sodium thiosulfate (8.16 g, 10.5 eq). The mixture was stirred for 30 min and the layers were separated. The ether layer was washed with an aqueous saturated solution of sodium bicarbonate (50 mL), water (50 mL), dried (sodium sulfate) and filtered. The filtrate was concentrated to give the crude (1-formyl-2-methyl-propyl)-carbamic acid tert-butyl ester used for the next step without further purification. The mixture was stirred for 30 min the layers were separated The ether layer was washed with an aqueous saturated solution of sodium bicarbonate (50 mL), water (50 mL) dried (sodium sulfate) filtered The filtrate was concentrated

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

Procedure: Method C was followed, using 5-(6-chloro-9H-β-carbolin-8-ylcarbamoyl)-2,2-dimethyl-morpholine-4-carboxylic acid tert-butyl ester and the appropriate aldehyde, (1-formyl-2-methyl-propyl)-carbamic acid tert-butyl ester.

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

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

Procedure: To a solution of Dess-Martin periodinane (3.12 g, 0.0073 mol, 1.5 eq) in dichloromethane (25 mL) was added a solution of N-Boc-L-valinol (1 g, 0.0049 mol, 1 eq) in dichloromethane (25 mL). The reaction mixture was stirred at room temperature for 3 h and was diluted with diethyl ether (50 mL). The mixture was poured into an aqueous saturated solution of sodium bicarbonate (100 mL) containing sodium thiosulfate (8.16 g, 10.5 eq). The mixture was stirred for 30 min and the layers were separated. The ether layer was washed with an aqueous saturated solution of sodium bicarbonate (50 mL), water (50 mL), dried (sodium sulfate) and filtered. The filtrate was concentrated to give the crude (1-formyl-2-methyl-propyl)-carbamic acid tert-butyl ester used for the next step without further purification. The mixture was stirred for 30 min the layers were separated The ether layer was washed with an aqueous saturated solution of sodium bicarbonate (50 mL), water (50 mL) dried (sodium sulfate) filtered The filtrate was concentrated

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

Procedure: Method C was followed, using 5-(6-chloro-9H-β-carbolin-8-ylcarbamoyl)-2,2-dimethyl-morpholine-4-carboxylic acid tert-butyl ester and the appropriate aldehyde, (1-formyl-2-methyl-propyl)-carbamic acid tert-butyl ester.

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

Procedure: To a solution of Dess-Martin periodinane (3.12 g, 0.0073 mol, 1.5 eq) in dichloromethane (25 mL) was added a solution of N-Boc-L-valinol (1 g, 0.0049 mol, 1 eq) in dichloromethane (25 mL). The reaction mixture was stirred at room temperature for 3 h and was diluted with diethyl ether (50 mL). The mixture was poured into an aqueous saturated solution of sodium bicarbonate (100 mL) containing sodium thiosulfate (8.16 g, 10.5 eq). The mixture was stirred for 30 min and the layers were separated. The ether layer was washed with an aqueous saturated solution of sodium bicarbonate (50 mL), water (50 mL), dried (sodium sulfate) and filtered. The filtrate was concentrated to give the crude (1-formyl-2-methyl-propyl)-carbamic acid tert-butyl ester used for the next step without further purification. The mixture was stirred for 30 min the layers were separated The ether layer was washed with an aqueous saturated solution of sodium bicarbonate (50 mL), water (50 mL) dried (sodium sulfate) filtered The filtrate was concentrated

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

Procedure: To a solution of Dess-Martin periodinane (3.12 g, 0.0073 mol, 1.5 eq) in dichloromethane (25 mL) was added a solution of N-Boc-L-valinol (1 g, 0.0049 mol, 1 eq) in dichloromethane (25 mL). The reaction mixture was stirred at room temperature for 3 h and was diluted with diethyl ether (50 mL). The mixture was poured into an aqueous saturated solution of sodium bicarbonate (100 mL) containing sodium thiosulfate (8.16 g, 10.5 eq). The mixture was stirred for 30 min and the layers were separated. The ether layer was washed with an aqueous saturated solution of sodium bicarbonate (50 mL), water (50 mL), dried (sodium sulfate) and filtered. The filtrate was concentrated to give the crude (1-formyl-2-methyl-propyl)-carbamic acid tert-butyl ester used for the next step without further purification. The mixture was stirred for 30 min the layers were separated The ether layer was washed with an aqueous saturated solution of sodium bicarbonate (50 mL), water (50 mL) dried (sodium sulfate) filtered The filtrate was concentrated