2-amino-N-benzylacetamide

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A suspension of N-benzylglycinamide (35.5 g, 0.22 mol) and ethyl 4-oxobutanoate (31 g, 0.24 mol) in toluene (370 ml) was refluxed for 6 hours in a Dean-Stark apparatus. After cooling, the mixture was extracted twice with 10% sulphuric acid (200+100 ml); the aqueous extracts were neutralized with sodium hydrogen carbonate and extracted twice with toluene (250 ml of each time). The organic solution was washed with water (100 ml), dried (MgSO4) and evaporated under vacuum to afford an oil which was triturated with a mixture of diethyl ether-light petroleum (1:2) to give 45 g (75%), of the title compound as a yellow solid, m.p. 60°-62° C. NMR (CDCl3): deltaH =7.5 (bs, 1H, NH); 7.30 (bs, 5H, PhH); 4.5-4.25 (ABX, 1H, CH--M); 4.13 (q, J=6.9 Hz, 2H, OCH2); 4.00 and 3.53 (ABq, J= 12.4 Hz, 2H, PhCH2); 3.37 and 3.02 (ABX, J=14.9 Hz, 2H, NCH2CO); 2.65-2.30 (c.a., 2H, CH2CH2CO); 2.20-1.15 (c.a., 2H, CH2CH2CO); 1.24 (t, J=6.9 Hz, 3H, CH3). MS (E.I., 70 eV, 1.5 mA) m/z=276 (M+), 231 (M--OEt)+, 185 (M--PhCH2)+, 175 (M--C5H9O2)+, 91 (PhCH2)+. was refluxed for 6 hours in a Dean-Stark apparatus After cooling the mixture was extracted twice with 10% sulphuric acid (200+100 ml) extracted twice with toluene (250 ml of each time) The organic solution was washed with water (100 ml) dried (MgSO4) evaporated under vacuum to afford an oil which was triturated with a mixture of diethyl ether-light petroleum (1:2) to give 45 g (75%)

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

実験手順: A suspension of N-benzylglycinamide (35.5 g, 0.22 mol) and ethyl 4-oxobutanoate (31g, 0.24 mol) in toluene (370 ml) was refluxed for 6 hours in a Dean-Stark apparatus. After cooling, the mixture was extracted twice with 10% sulphuric acid (200+100 ml); the aqueous extracts were neutralized with sodium hydrogen carbonate and extracted twice with toluene (250 ml each time). The organic solution was washed with water (100 ml), dried (MgSO4) and evaporated under vacuum to afford an oil which was triturated with a mixture of diethyl ether -light petroleum (1:2) to give 45 g (75%), of the title compound as a yellow solid, m.p. 60°-62° C. NMR (CDCl3): deltaH =7.5 (bs, 1H, NH); 7.30 (bs, 5H, PhH); 4.5-4.25 (ABX, 1H, CH--M); 4.13 (q, J=6.9 Hz, 2H, OCH2); 4.00 and 3.53 (ABq, J=12.4 Hz, 2H, PhCH2); 3.37 and 3.02 (ABX, J=14.9 Hz, 2H, NCH2CO); 2.65-2.30 (c.a., 2H, CH2CH2CO); 2.20-1.15 (c.a., 2H, CH2CH2CO); 1.24 (t, J=6.9 Hz, 3H, CH3). MS (E.I., 70 eV, 1.5 mA) m/z=276 (M+), 231 (M--OEt)+, 185 (M--PhCH2)+, 175 (M - C5H9O2)+, 91 (PhCH2)+. was refluxed for 6 hours in a Dean-Stark apparatus After cooling the mixture was extracted twice with 10% sulphuric acid (200+100 ml) extracted twice with toluene (250 ml each time) The organic solution was washed with water (100 ml) dried (MgSO4) evaporated under vacuum to afford an oil which was triturated with a mixture of diethyl ether -light petroleum (1:2) to give 45 g (75%)

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

実験手順: A suspension of N-benzylglycinamide (35.5 g, 0.22 mol) and ethyl 4-oxobutanoate (31 g, 0.24 mol) in toluene (370 ml) was refluxed for 6 hours in a Dean-Stark apparatus. After cooling, the mixture was extracted twice with 10% sulphuric acid (200+100 ml); the aqueous extracts were neutralized with sodium hydrogen carbonate and extracted twice with toluene (250 ml of each time). The organic solution was washed with water (100 ml), dried (MgSO4) and evaporated under vacuum to afford an oil which was triturated with a mixture of diethyl ether-light petroleum (1:2) to give 45 g (75%), of the title compound as a yellow solid, m.p. 60°-62° C. NMR (CDCl3): deltaH =7.5 (bs, 1H, NH); 7.30 (bs, 5H, PhH); 4.5-4.25 (ABX, 1H, CH--M); 4.13 (q, J=6.9 Hz, 2H, OCH2); 4.00 and 3.53 (ABq, J= 12.4 Hz, 2H, PhCH2); 3.37 and 3.02 (ABX, J=14.9 Hz, 2H, NCH2CO); 2.65-2.30 (c.a., 2H, CH2CH2CO); 2.20-1.15 (c.a., 2H, CH2CH2CO); 1.24 (t, J=6.9 Hz, 3H, CH3). MS (E.I., 70 eV, 1.5 mA) m/z=276 (M+), 231 (M--OEt)+, 185 (M--PhCH2)+, 175 (M--C5H9O2)+, 91 (PhCH2)+. was refluxed for 6 hours in a Dean-Stark apparatus After cooling the mixture was extracted twice with 10% sulphuric acid (200+100 ml) extracted twice with toluene (250 ml of each time) The organic solution was washed with water (100 ml) dried (MgSO4) evaporated under vacuum to afford an oil which was triturated with a mixture of diethyl ether-light petroleum (1:2) to give 45 g (75%)

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

実験手順: A suspension of N-benzylglycinamide (35.5 g, 0.22 mol) and ethyl 4-oxobutanoate (31 g, 0.24 mol) in toluene (370 ml) was refluxed for 6 hours in a Dean-Stark apparatus. After cooling, the mixture was extracted twice with 10% sulphuric acid (200+100 ml); the aqueous extracts were neutralized with sodium hydrogen carbonate and extracted twice with toluene (250 ml of each time). The organic solution was washed with water (100 ml), dried (MgSO4) and evaporated under vacuum to afford an oil which was triturated with a mixture of diethyl ether-light petroleum (1:2) to give 45 g (75%), of the title compound as a yellow solid, m.p. 60°-62° C. NMR (CDCl3): deltaH =7.5 (bs, 1H, NH); 7.30 (bs, 5H, PhH); 4.5-4.25 (ABX, 1H, CH--M); 4.13 (q, J=6.9 Hz, 2H, OCH2); 4.00 and 3.53 (ABq, J= 12.4 Hz, 2H, PhCH2); 3.37 and 3.02 (ABX, J=14.9 Hz, 2H, NCH2CO); 2.65-2.30 (c.a., 2H, CH2CH2CO); 2.20-1.15 (c.a., 2H, CH2CH2CO); 1.24 (t, J=6.9 Hz, 3H, CH3). MS (E.I., 70 eV, 1.5 mA) m/z=276 (M+), 231 (M--OEt)+, 185 (M--PhCH2)+, 175 (M--C5H9O2)+, 91 (PhCH2)+. was refluxed for 6 hours in a Dean-Stark apparatus After cooling the mixture was extracted twice with 10% sulphuric acid (200+100 ml) extracted twice with toluene (250 ml of each time) The organic solution was washed with water (100 ml) dried (MgSO4) evaporated under vacuum to afford an oil which was triturated with a mixture of diethyl ether-light petroleum (1:2) to give 45 g (75%)

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Using the procedure described in example 3, a solution of 1-(2-adamantan-1-yl-2-oxoethyl) L-proline (104.6 mg, 0.36 mmol, 1.0 eq), triethylamine (150 uL, 1.07 mmol, 3.0 eq), and THF (1.5 mL), was treated with isobutyl chloroformate (51 uL, 0.39 mL, 1.1 eq), then with glycine N-benzylamide (88.2 mg, 537 umol, 1.5 eq). Workup as before provided 53.9 mg (34%) of glycine, N-[1-(2-adamantan-1-yl-2-oxoethyl)-L-prolyl] benzylamide. as a white foam.

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

実験手順: Using the procedure described in example 3, a solution of 1-(2-adamantan-1-yl-2-oxoethyl) L-proline (104.6 mg, 0.36 mmol, 1.0 eq), triethylamine (150 uL, 1.07 mmol, 3.0 eq), and THF (1.5 mL), was treated with isobutyl chloroformate (51 uL, 0.39 mL, 1.1 eq), then with glycine N-benzylamide (88.2 mg, 537 umol, 1.5 eq). Workup as before provided 53.9 mg (34%) of glycine, N-[1-(2-adamantan-1-yl-2-oxoethyl)-L-prolyl] benzylamide. as a white foam.

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

実験手順: Using the procedure described in example 3, a solution of 1-(2-adamantan-1-yl-2-oxoethyl) L-proline (104.6 mg, 0.36 mmol, 1.0 eq), triethylamine (150 uL, 1.07 mmol, 3.0 eq), and THF (1.5 mL), was treated with isobutyl chloroformate (51 uL, 0.39 mL, 1.1 eq), then with glycine N-benzylamide (88.2 mg, 537 umol, 1.5 eq). Workup as before provided 53.9 mg (34%) of glycine, N-[1-(2-adamantan-1-yl-2-oxoethyl)-L-prolyl] benzylamide. as a white foam.

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

実験手順: To a solution of N1-benzylglycinamide (3.00 g, 14.95 mmol) in MeOH (25 mL) were added acetone (5.50 mL, 74.75 mmol) and triethylamine (1.67 mL, 11.96 mmol). The solution was stirred and heated to reflux overnight under an atmosphere of nitrogen. The solvent was removed in vacuo, and the resulting orange oil was purified by flash column chromatography on silica gel using a gradient elution of 0-7% (MeOH/NH3)/CH2Cl2. Collection and concentration of the appropriate fractions afforded the product as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.31-7.27 (m, 5H), 4.44 (s, 2H), 3.55 (s, 2H), 1.26 (s, 6H); ES MS (M+1)=205. heated to reflux overnight under an atmosphere of nitrogen The solvent was removed in vacuo the resulting orange oil was purified by flash column chromatography on silica gel using a gradient elution of 0-7% (MeOH/NH3)/CH2Cl2 Collection and concentration of the appropriate fractions

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

実験手順: A suspension of N-benzylglycinamide (35.5 g, 0.22 mol) and ethyl 4-oxobutanoate (31 g, 0.24 mol) in toluene (370 ml) was refluxed for 6 hours in a Dean-Stark apparatus. After cooling, the mixture was extracted twice with 10% sulphuric acid (200+100 ml); the aqueous extracts were neutralized with sodium hydrogen carbonate and extracted twice with toluene (250 ml each time). The organic solution was washed with water (100 ml), dried (MgSO4) and evaporated under vacuum to afford an oil which was triturated with a mixture of diethyl ether-light petroleum (1:2) to give 45 g (75%), of the title compound as a yellow solid, m.p. 60°-62° C. NMR (CDCl3): deltaH =7.5 (bs, 1H, NH); 7.30 (bs, 5H, PhH); 4.5-4.25 (ABX, 1H, CH-M); 4.13 (q, J=6.9 Hz, 2H, OCH2); 4.00 and 3.53 (ABq, J=12.4 Hz, 2H, PhCH2); 3.37 and 3.02 (ABX, J=14.9 Hz, 2H, NCH2CO); 2.65-2.30 (c.a., 2H, CH2CH2CO); 2.20-1.15 (c.a., 2H, CH2CH2CO); 1.24 (t, J=6.9 Hz, 3H, CH3). MS (E.I., 70 eV, 1.5 mA) m/z=276 (M+), 231 (M-OEt)+, 185 (M-PhCH2)+, 175 (M-C5H9O2)+, 91 (PhCH2)+. was refluxed for 6 hours in a Dean-Stark apparatus After cooling the mixture was extracted twice with 10% sulphuric acid (200+100 ml) extracted twice with toluene (250 ml each time) The organic solution was washed with water (100 ml) dried (MgSO4) evaporated under vacuum to afford an oil which was triturated with a mixture of diethyl ether-light petroleum (1:2) to give 45 g (75%)

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

実験手順: A suspension of N-benzylglycinamide (35.5 g, 0.22 mol) and ethyl 4-oxobutanoate (31g, 0.24 mol) in toluene (370 ml) was refluxed for 6 hours in a Dean-Stark apparatus. After cooling, the mixture was extracted twice with 10% sulphuric acid (200+100 ml); the aqueous extracts were neutralized with sodium hydrogen carbonate and extracted twice with toluene (250 ml each time). The organic solution was washed with water (100 ml), dried (MgSO4) and evaporated under vacuum to afford an oil which was triturated with a mixture of diethyl ether -light petroleum (1:2) to give 45 g (75%), of the title compound as a yellow solid, m.p. 60°-62° C. NMR (CDCl3): deltaH =7.5 (bs, 1H, NH); 7.30 (bs, 5H, PhH); 4.5-4.25 (ABX, 1H, CH--M); 4.13 (q, J=6.9 Hz, 2H, OCH2); 4.00 and 3.53 (ABq, J=12.4 Hz, 2H, PhCH2); 3.37 and 3.02 (ABX, J=14.9 Hz, 2H, NCH2CO); 2.65-2.30 (c.a., 2H, CH2CH2CO); 2.20-1.15 (c.a., 2H, CH2CH2CO); 1.24 (t, J=6.9 Hz, 3H, CH3). MS (E.I., 70 eV, 1.5 mA) m/z=276 (M+), 231 (M--OEt)+, 185 (M--PhCH2)+, 175 (M - C5H9O2)+, 91 (PhCH2)+. was refluxed for 6 hours in a Dean-Stark apparatus After cooling the mixture was extracted twice with 10% sulphuric acid (200+100 ml) extracted twice with toluene (250 ml each time) The organic solution was washed with water (100 ml) dried (MgSO4) evaporated under vacuum to afford an oil which was triturated with a mixture of diethyl ether -light petroleum (1:2) to give 45 g (75%)