4-prop-2-ynoxybenzaldehyde

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 6-aminohexanoic acid (2.62 g, 20 mmol), 4-(prop-2-yn-1-yloxy)benzaldehyde (0.80 g, 5.0 mmol) and acetic acid (0.50 mL) in DCE (50 mL) was heated at 80° C. for 60 min. The reaction mixture was cooled to 0° C., and treated with NaBH(OAc)3 (2.11 g, 10 mmol). The reaction was stirred at room temperature for 12 hours and decomposed with water and then extracted with DCM. The organic layer was dried and concentrated under reduced pressure to give a residue, which was purified using a Biotage SP4 and gradient elution of 5-50% methanol in DCM. The yield of the target compound 6-((4-(prop-2-yn-1-yloxy)benzyl)amino)hexanoic acid was 62% (0.856 g). 1H NMR (400 MHz, DMSO-d6): δ 7.19 (d, J=8.4 Hz, 2H), 6.86 (d, J=8.4 Hz, 2H), 4.71 (s, 2H), 3.56 (s, 2H), 3.49 (s, 1H), 2.39 (t, J=7.0 Hz, 2H), 2.00 (t, J=7.2 Hz, 2H), 1.41-1.19 (m, 6H); MS (ESI), 276.1 (M+H)+. extracted with DCM The organic layer was dried concentrated under reduced pressure to give a residue, which was purified a Biotage SP4 and gradient elution of 5-50% methanol in DCM

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred suspension of 4-hydroxybenzaldehyde (425.8 g) and K2CO3 (807.6 g) in acetone (2,960 ml) at reflux temper-ature of about 60° C. under a nitrogen atmosphere, was added dropwise 3-bromo-propyne (502.4 g) over a period of 2 hours. The reaction was heated at reflux for 3 more hours. After cooling to room temperature the reaction mixture was filtered and the excess of K2CO3 removed and washed several times with acetone. The filtrate was washed with saturated aqueous solution of NaHCO2 and NaCl. The aqueous phase was extracted with diethyl ether. The combined organic extracts were dried over Na2SO4, filtered and concentrated to a volume of 1 liter. The solution was kept in the refrigerator overnight. The crystals were filtered out and washed with cold diethyl ether. The filtrate was kept in the refrigerator and some more crystals were formed and removed. This procedure was repeated 3 times resulting in 1,385.26 g of 4-(2-propynyloxy) benzaldehyde in 83% yield. The material was analysed by gas chromatography, and shown to be 99.9% pure. Infrared and mass spectroscopic analysis confirmed the structure. The reaction was heated at reflux for 3 more hours After cooling to room temperature the reaction mixture was filtered the excess of K2CO3 removed washed several times with acetone The filtrate was washed with saturated aqueous solution of NaHCO2 and NaCl The aqueous phase was extracted with diethyl ether The combined organic extracts were dried over Na2SO4 filtered concentrated to a volume of 1 liter was kept in the refrigerator overnight The crystals were filtered out washed with cold diethyl ether some more crystals were formed removed

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred suspension of 4-hydroxybenzaldehyde (425.8 g) and K2CO3 (807.6 g) in acetone (2,960 ml) at reflux temper-ature of about 60° C. under a nitrogen atmosphere, was added dropwise 3-bromo-propyne (502.4 g) over a period of 2 hours. The reaction was heated at reflux for 3 more hours. After cooling to room temperature the reaction mixture was filtered and the excess of K2CO3 removed and washed several times with acetone. The filtrate was washed with saturated aqueous solution of NaHCO3 and NaCl. The aqueous phase was extracted with diethyl ether. The combined organic extracts were dried over Na2SO4, filtered and concentrated to a volume of 1 liter. The solution was kept in the refrigerator overnight. The crystals were filtered out and washed with cold diethyl ether. The filtrate was kept in the refrigerator and some more crystals were formed and removed. This procedure was repeated 3 times resulting in 1,385.26 g of 4-(2-propynyloxy) benzaldehyde in 83% yield. The material was analysed by gas chromatography, and shown to be 99.9% pure. Infrared and mass spectroscopic analysis confirmed the structure. The reaction was heated at reflux for 3 more hours After cooling to room temperature the reaction mixture was filtered the excess of K2CO3 removed washed several times with acetone The filtrate was washed with saturated aqueous solution of NaHCO3 and NaCl The aqueous phase was extracted with diethyl ether The combined organic extracts were dried over Na2SO4 filtered concentrated to a volume of 1 liter was kept in the refrigerator overnight The crystals were filtered out washed with cold diethyl ether some more crystals were formed removed

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

実験手順: A mixture of 4-ethynylbenzaldehyde (1) (171 mg, 1.27 mmol), methyl 3-oxopentanoate (175 mg, 1.27 mmol), dimedone (181 mg, 1.27 mmol), ammonium acetate (101 mg, 1.27 mmol), I2 (97 mg, 0.38 mmol), and ethanol (10 drops) is stirred under argon for 5.5 h, quenched with 5% Na2S2O3 (30 mL), and extracted with ethyl acetate (50 mL and 30 mL). The extract is washed (5% Na2S2O3, H2O, and brine) and dried. After solvent removal at reduced pressure, the residue is purified on silica gel (33% to 60% ethyl acetate/hexane) to give 277 mg (60%) of 2 (BI-3029) as a cream solid, mp 234-236° C. IR 3332, 2933, 1704, 1610, 1482, 1214 cm−1; 1H NMR (CDCl3) δ 0.93 (s, 3H, CH3), 1.10 (s, 3H, CH3), 1.26 (t, J=7.2 Hz, 3H, CH2CH3), 2.07-2.42 (m, 4H, COCH2, CH2), 2.76-2.89 (m, 2H, CH2CH3), 3.02 (s, 1H, CH≡C), 3.63 (s, 3H, OCH3), 5.09 (s, 1H, CH), 5.90 (bs, 1H, NH), 7.27 (d, J=8.1 Hz, 2H, 3,5-ArH), 7.37 ppm (d, J=8.1 Hz, 2H, 2,6-ArH). quenched with 5% Na2S2O3 (30 mL) extracted with ethyl acetate (50 mL and 30 mL) The extract is washed (5% Na2S2O3, H2O, and brine) dried After solvent removal at reduced pressure the residue is purified on silica gel (33% to 60% ethyl acetate/hexane)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 6-aminohexanoic acid (2.62 g, 20 mmol), 4-(prop-2-yn-1-yloxy)benzaldehyde (0.80 g, 5.0 mmol) and acetic acid (0.50 mL) in DCE (50 mL) was heated at 80° C. for 60 min. The reaction mixture was cooled to 0° C., and treated with NaBH(OAc)3 (2.11 g, 10 mmol). The reaction was stirred at room temperature for 12 hours and decomposed with water and then extracted with DCM. The organic layer was dried and concentrated under reduced pressure to give a residue, which was purified using a Biotage SP4 and gradient elution of 5-50% methanol in DCM. The yield of the target compound 644-(prop-2-yn-1-yloxy)benzyl)amino)hexanoic acid was 62% (0.856 g). 1H NMR (400 MHz, DMSO-d6): δ 7.19 (d, J=8.4 Hz, 2H), 6.86 (d, J=8.4 Hz, 2H), 4.71 (s, 2H), 3.56 (s, 2H), 3.49 (s, 1H), 2.39 (t, J=7.0 Hz, 2H), 2.00 (t, J=7.2 Hz, 2H), 1.41-1.19 (m, 6H); MS (ESI), 276.1 (M+H)+. extracted with DCM The organic layer was dried concentrated under reduced pressure to give a residue, which was purified a Biotage SP4 and gradient elution of 5-50% methanol in DCM

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 6-aminohexanoic acid (2.62 g, 20 mmol), 4-(prop-2-yn-1-yloxy)benzaldehyde (0.80 g, 5.0 mmol) and acetic acid (0.50 mL) in DCE (50 mL) was heated at 80° C. for 60 min. The reaction mixture was cooled to 0° C., and treated with NaBH(OAc)3 (2.11 g, 10 mmol). The reaction was stirred at room temperature for 12 hours and decomposed with water and then extracted with DCM. The organic layer was dried and concentrated under reduced pressure to give a residue, which was purified using a Biotage SP4 and gradient elution of 5-50% methanol in DCM. The yield of the target compound 6-((4-(prop-2-yn-1-yloxy)benzyl)amino)hexanoic acid was 62% (0.856 g). 1H NMR (400 MHz, DMSO-d6): δ 7.19 (d, J=8.4 Hz, 2H), 6.86 (d, J=8.4 Hz, 2H), 4.71 (s, 2H), 3.56 (s, 2H), 3.49 (s, 1H), 2.39 (t, J=7.0 Hz, 2H), 2.00 (t, J=7.2 Hz, 2H), 1.41-1.19 (m, 6H); MS (ESI), 276.1 (M+H)+. extracted with DCM The organic layer was dried concentrated under reduced pressure to give a residue, which was purified a Biotage SP4 and gradient elution of 5-50% methanol in DCM