Carbamic acid, (4-oxopentyl)-, 1,1-dimethylethyl ester (9CI)

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 11-4 (5.0 g, 24.8 mmol), 1-3, 2-amino-3-formylpyridine (3.6 g, 29.8 mmol) and 20% KOH (1 ml) in absolute ethanol (100 mL) was heated at reflux for 8 h. Following evaporative removal of the solvent, the residue was chromatographed (silica gel, 70:28:2 chloroform/ethyl acetate/methanol) to give 11-6 as a yellow oil. was heated at reflux for 8 h removal of the solvent the residue was chromatographed (silica gel, 70:28:2 chloroform/ethyl acetate/methanol)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 11-3 (10.0 g, 40.5 mmol) and THF (200 ml) at 0° C. was added methylmagnesium bromide (27.0 ml, 91.0 mmol; 3M in ether) dropwise over 20 minutes. After 2.0 hours, 10% KHSO4 was added slowly. The mixture was extracted with EtOAc. The organic portion was washed with sat. NaHCO3, brine, and dried over MgSO4. Evaporative removal of the solvent gave 11-4 as a colorless oil. The mixture was extracted with EtOAc The organic portion was washed with sat. NaHCO3, brine dried over MgSO4 Evaporative removal of the solvent

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of pyrrolidine (79 mg, 1.11 mmol) in dry CH3CN (6 mL) was added tert-butyl (4-oxopentyl)carbamate (291 mg, 1.44 mmol) followed by Na(OAc)3BH (680 mg, 2.88 mmol) at rt. The reaction mixture was stirred at rt until completion of the reaction. Sat. aq. NaHCO3 was then added and the mixture extracted with EA (3×). The combined org. extracts were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by FC(CH2Cl2-MeOH—NH3) to give pure N-tert-butoxycarbonyl-4-(pyrrolidin-1-yl)pentan-1-amine as a colorless oil. LC-MS-conditions 05c: tR=0.53 min; [M+H]+=257.41. The title compound was obtained after Boc deprotection using 4N HCl in dioxane (10.0 eq.) in CH2Cl2 at rt as a colorless oil. the mixture extracted with EA (3×) extracts were dried over MgSO4 filtered concentrated under reduced pressure The crude residue was purified by FC(CH2Cl2-MeOH—NH3)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of 4-(tert-butoxycarbonyl-amino)butyric acid (1.00 g, 4.77 mmol) in dry CH3CN (24 mL) were added N,O-dimethyl-hydroxylamine hydrochloride (475 mg, 4.77 mmol), EDC.HCl (934 mg, 4.77 mmol), HOBt (658 mg, 4.77 mmol) and N-methylmorpholine (2.68 mL, 23.86 mmol) at rt. The reaction mixture was stirred at rt until completion of the reaction. The mixture was then concentrated under reduced pressure. The residue was redissolved in EA, successively washed with water, 10% aq. KHSO4, sat. aq. NaHCO3 and brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was dissolved in dry THF (20 mL) and treated with MeMgBr (3.0M solution in Et2O, 3.25 mL, 9.75 mmol) at 0° C. The reaction mixture was stirred at 0° C. until completion of the reaction. 10% Aq. KHSO4 was then carefully added, the layers separated and the aq. layer extracted with EA (3×). The combined org. extracts were successively washed with aq. sat. NaHCO3 and brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by FC (hept-EA 3:2) to give the title compound as a colorless oil. TLC:rf (3:2 hept-EA)=0.38. The mixture was then concentrated under reduced pressure The residue was redissolved in EA successively washed with water, 10% aq. KHSO4, sat. aq. NaHCO3 and brine dried over MgSO4 filtered concentrated under reduced pressure The crude material was dissolved in dry THF (20 mL) The reaction mixture was stirred at 0° C. until completion of the reaction the layers separated the aq. layer extracted with EA (3×) extracts were successively washed with aq. sat. NaHCO3 and brine dried over MgSO4 filtered concentrated under reduced pressure The crude residue was purified by FC (hept-EA 3:2)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 11-4 (5.0 g, 24.8 mmol), 1-3, 2-amino-3-formylpyridine (3.6 g, 29.8 mmol) and 20% KOH (1 ml) in absolute ethanol (100 mL) was heated at reflux for 8 h. Following evaporative removal of the solvent, the residue was chromatographed (silica gel, 70:28:2 chloroform/ethyl acetate/methanol) to give 11-6 as a yellow oil. was heated at reflux for 8 h removal of the solvent the residue was chromatographed (silica gel, 70:28:2 chloroform/ethyl acetate/methanol)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 11-3 (10.0 g, 40.5 mmol) and THF (200 ml) at 0° C. was added methylmagnesium bromide (27.0 ml, 91.0 mmol; 3M in ether) dropwise over 20 minutes. After 2.0 hours, 10% KHSO4 was added slowly. The mixture was extracted with EtOAc. The organic portion was washed with sat. NaHCO3, brine, and dried over MgSO4. Evaporative removal of the solvent gave 11-4 as a colorless oil. The mixture was extracted with EtOAc The organic portion was washed with sat. NaHCO3, brine dried over MgSO4 Evaporative removal of the solvent

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 11-3 (10.0 g, 40.5 mmol) and THF (200 ml) at 0° C. was added methylmagnesium bromide (27.0 ml, 91.0 mmol; 3M in ether) dropwise over 20 minutes. After 2.0 hours, 10% KHSO4 was added slowly. The mixture was extracted with EtOAc. The organic portion was washed with sat. NaHCO3, brine, and dried over MgSO4. Evaporative removal of the solvent gave 11-4 as a colorless oil. The mixture was extracted with EtOAc The organic portion was washed with sat. NaHCO3, brine dried over MgSO4 Evaporative removal of the solvent

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 11-4 (5.0 g, 24.8 mmol), 1-3, 2-amino-3-formylpyridine (3.6 g, 29.8 mmol) and 20% KOH (1 ml) in absolute ethanol (100 mL) was heated at reflux for 8 h. Following evaporative removal of the solvent, the residue was chromatographed (silica gel, 70:28:2 chloroform/ethyl acetate/methanol) to give 11-6 as a yellow oil. was heated at reflux for 8 h removal of the solvent the residue was chromatographed (silica gel, 70:28:2 chloroform/ethyl acetate/methanol)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 11-4 (5.0 g, 24.8 mmol), 1-3, 2-amino-3-formylpyridine (3.6 g, 29.8 mmol) and 20% KOH (1 ml) in absolute ethanol (100 mL) was heated at reflux for 8 h. Following evaporative removal of the solvent, the residue was chromatographed (silica gel, 70:28:2 chloroform/ethyl acetate/methanol) to give 11-6 as a yellow oil. was heated at reflux for 8 h removal of the solvent the residue was chromatographed (silica gel, 70:28:2 chloroform/ethyl acetate/methanol)