benzyl N-prop-2-ynylcarbamate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of hydantoin 2 (830 mg, 2 mmol), N-Cbz-propargylamine (460 mg, 2.43 mmol; prepared according to the literature by Yasuda et al., patent application 2003, US 2003/0004353), CuI (20 mg, 0.1 mmol), PdCl2(PPh3)2 (70 mg, 0.1 mmol) and iPr2NH (850 μL, 6 mmol) in DMF (5 mL) was heated for 15 min at 100° C. (Smith Microwave Synthesizer). The reaction mixture was diluted with EtOAc, washed with 1 M HCl (2×), NaHCO3 (1×), water (3×) and brine (1×), then dried over MgSO4, filtered and concentrated under vacuum. The crude material was subjected to silica gel chromatography (30→50% EtOAc/hexanes) to yield the desired material as a colorless film (598 mg, 57%). 1H NMR (400 MHz, CDCl3) δ 7.89 (m, 2H), 7.21-7.46 (m, 12H), 6.71 (bs, 1H), 4.62 (s, 2H), 4.12 (m, 2H), 3.81 (s, 3H), 1.72 (s, 3H). MS (ES+): 526 (M+H). prepared washed with 1 M HCl (2×), NaHCO3 (1×), water (3×) and brine (1×) dried over MgSO4 filtered concentrated under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of propargylamine (6.4 g, 71.2 mmol) in pyridine (100 mL) was added benzylchloroformate (13.37 g, 78.2 mmol) in 100 mL CH2Cl2 over 0.5 h. The reaction was stirred for 16 h and the volatiles were removed in vacuo. The residue was dissolved in EtOAc and the organic solution was washed with water (2×). The organic solution was washed with dilute aqueous HCl followed by saturated NaHCO3. The organic solution was dried over MgSO4, filtered, and concentrated in vacuo to provide the title compound (4.43 g). the volatiles were removed in vacuo The residue was dissolved in EtOAc the organic solution was washed with water (2×) The organic solution was washed with dilute aqueous HCl The organic solution was dried over MgSO4 filtered concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound of Step B was prepared from prop-2-ynyl-carbamic acid benzyl ester and 5-bromo-thiophene-2-carboxylic acid tert-butyl ester in an analagous manner to Step A of Preparation 2.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of propargylamine (6.4 g, 71.2 mmol) in pyridine (100 mL) was added benzylchloroformate (13.37 g, 78.2 mmol) in 100 mL CH2Cl2over 0.5 h. The reaction benzylchloroformate (13.37 g, 78.2 mmol) in 100 mL CH2Cl2over0.5 h. The reaction dissolved in EtOAc and the organic solution was washed with water (2×). The organic solution was washed with dilute aqueous HCl followed by saturated NaHCO3. The organic solution was dried over MgSO4, filtered, and concentrated in vacuo to provide the title compound (4.43 g). 5 h the organic solution was washed with water (2×) The organic solution was washed with dilute aqueous HCl The organic solution was dried over MgSO4 filtered concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of propargylamine (6.4 g, 71.2 mmol) in pyridine (100 mL) was added benzylchloroformate (13.37 g, 78.2 mmol) in 100 mL CH2Cl2over 0.5 h. The reaction benzylchloroformate (13.37 g, 78.2 mmol) in 100 mL CH2Cl2over0.5 h. The reaction dissolved in EtOAc and the organic solution was washed with water (2×). The organic solution was washed with dilute aqueous HCl followed by saturated NaHCO3. The organic solution was dried over MgSO4, filtered, and concentrated in vacuo to provide the title compound (4.43 g). 5 h the organic solution was washed with water (2×) The organic solution was washed with dilute aqueous HCl The organic solution was dried over MgSO4 filtered concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2,5-dibromopyridine (1.19 g), N-Boc-propargylamine (781 mg), Pd(PPh3)2Cl2 (73 mg), and CuI (10 mg) in diisopropylamine (20 mL) was stirred at room temperature overnight under nitrogen atmosphere. To the mixture was added N-Cbz-propargylamine (1.14 g) and the mixture was heated under reflux temperature for 5 hours under nitrogen atmosphere. The mixture was cooled to room temperature. To the mixture was added ethyl acetate (50 mL). The precipitates were filtered and washed with ethyl acetate. The filtrate and washings were combined and purified by silica gel column to give 6-1 (250 mg) as a crystalline compound. the mixture was heated under reflux temperature for 5 hours under nitrogen atmosphere The mixture was cooled to room temperature The precipitates were filtered washed with ethyl acetate purified by silica gel column

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2,5-dibromopyridine (3.00 g), N-Cbz-propargylamine (5.99 g), PdCl2(PPh3)2 (89.8 mg), and CuI (6.0 mg) in diisopropylamine (51 ml) was heated at 65° C. for 7 hours under nitrogen atmosphere. The mixture was cooled to room temperature, and the precipitates were filtered, washed with water, and dried under reduced pressure to give 8-1 (4.96 g) as a crystalline compound; m.p. 156-158° C. The mixture was cooled to room temperature the precipitates were filtered washed with water dried under reduced pressure