3-酞酰亚胺基丙酸甲酯

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

实验步骤: Prepared in 17% yield (44 mg) as described in general procedure (K) from 2-(3,3-dicyclohexylureido)-thiazole-4-carboxylic acid (210 mg, 0.60 mmol) and (S)-alanine methyl ester (HCl salt, 84 mg, 0.6 mmol). Prepared in 17% yield (44 mg)

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

实验步骤: Prepared in 17% yield (44 mg) as described in general procedure (K) from 2-(3,3-dicyclohexylureido)-thiazole-4-carboxylic acid (210 mg, 0.60 mmol) and (S)-alanine methyl ester (HCl salt, 84 mg, 0.6 mmol). Prepared in 17% yield (44 mg)

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

实验步骤: 0.030 g of 6-isopropoxy-1-chloro-4-hydroxy-isoquinoline-3-carboxylic acid and 0.046 g of HATU were allowed to react with 0.017 g of L-Alanine methyl ester under analogous conditions to Example A-1 a). Treatment of the crude product ester with 0.014 g of NaOH in 0.1 ml of 1:1 methanol-water at room temperature for 2 days, followed by acidification to pH=2 with 1M hydrochloric acid, gave a solid product. The product was collected by filtration, washed with water, and dried to give 0.023 g of an off-white solid: MS-(−)-ion, M−1=353.0 amu. gave a solid product The product was collected by filtration washed with water dried

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

实验步骤: 0.030 g of 6-isopropoxy-1-chloro-4-hydroxy-isoquinoline-3-carboxylic acid and 0.046 g of HATU were allowed to react with 0.017 g of L-Alanine methyl ester under analogous conditions to Example A-1 a). Treatment of the crude product ester with 0.014 g of NaOH in 0.1 ml of 1:1 methanol-water at room temperature for 2 days, followed by acidification to pH=2 with 1M hydrochloric acid, gave a solid product. The product was collected by filtration, washed with water, and dried to give 0.023 g of an off-white solid: MS-(−)-ion, M−1=353.0 amu. gave a solid product The product was collected by filtration washed with water dried

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

实验步骤: 25 g of H-Ala-OMe, HCl and 66 g. of Boc-Ser-ONb are dissolved in 500 ml DMF. The product is cooled in an ice bath and 25 ml of NEM, 24 g of N-hydroxy benzotriazole are added wtih magnetic stirring and the pH is maintained at 6.5 or 7 by addition of NEM. The product is stirred for 18 hrs. at ambient temperature. After TLC monitoring, the medium is evaporated to 90% (13.33 Pa 35° C.). The oil obtained is dissolved in 1.500 ml of chloroform, the product is washed with a solution of saturated sodium chloride (twice), 5% potassium sulfate/bisulfate solution (3 times), saturated sodium bicarbonate (5 times). The solution is dried over Na2 `SO4 and evaporated to dryness. An oil is obtained which is dried to constant weight (30° C.13.33 Pa) The product is cooled in an ice bath the pH is maintained at 6.5 or 7 by addition of NEM The product is stirred for 18 hrs at ambient temperature After TLC monitoring, the medium is evaporated to 90% (13.33 Pa 35° C.) The oil obtained the product is washed with a solution of saturated sodium chloride (twice), 5% potassium sulfate/bisulfate solution (3 times), saturated sodium bicarbonate (5 times) The solution is dried over Na2 `SO4 evaporated to dryness An oil is obtained which is dried to constant weight (30° C.13.33 Pa)

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

实验步骤: 25 g of H-Ala-OMe, HCl and 66 g. of Boc-Ser-ONb are dissolved in 500 ml DMF. The product is cooled in an ice bath and 25 ml of NEM, 24 g of N-hydroxy benzotriazole are added wtih magnetic stirring and the pH is maintained at 6.5 or 7 by addition of NEM. The product is stirred for 18 hrs. at ambient temperature. After TLC monitoring, the medium is evaporated to 90% (13.33 Pa 35° C.). The oil obtained is dissolved in 1.500 ml of chloroform, the product is washed with a solution of saturated sodium chloride (twice), 5% potassium sulfate/bisulfate solution (3 times), saturated sodium bicarbonate (5 times). The solution is dried over Na2 `SO4 and evaporated to dryness. An oil is obtained which is dried to constant weight (30° C.13.33 Pa) The product is cooled in an ice bath the pH is maintained at 6.5 or 7 by addition of NEM The product is stirred for 18 hrs at ambient temperature After TLC monitoring, the medium is evaporated to 90% (13.33 Pa 35° C.) The oil obtained the product is washed with a solution of saturated sodium chloride (twice), 5% potassium sulfate/bisulfate solution (3 times), saturated sodium bicarbonate (5 times) The solution is dried over Na2 `SO4 evaporated to dryness An oil is obtained which is dried to constant weight (30° C.13.33 Pa)

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

实验步骤: 25 g of H-Ala-OMe, HCl and 66 g. of Boc-Ser-ONb are dissolved in 500 ml DMF. The product is cooled in an ice bath and 25 ml of NEM, 24 g of N-hydroxy benzotriazole are added with magnetic stirring and the pH is maintained at 6.5 or 7 by addition of NEM. The product is stirred for 18 hrs. at ambient temperature. After TLC monitoring, the medium is evaporated to 90% (0.1 mm Hg-35° C.). The oil obtained is dissolved in 1.500 ml of chloroform, the product is washed with a solution of saturated sodium chloride (twice), 5% sulfate/potassium bisulfate solution (3 times), saturated sodium bicarbonate (5 times). The solution is dried over Na2SO4 and evaporated to dryness. An oil is obtained which is dried to constant weight (30°-0.1 mm Hg). The product is cooled in an ice bath the pH is maintained at 6.5 or 7 by addition of NEM The product is stirred for 18 hrs at ambient temperature After TLC monitoring, the medium is evaporated to 90% (0.1 mm Hg-35° C.) The oil obtained the product is washed with a solution of saturated sodium chloride (twice), 5% sulfate/potassium bisulfate solution (3 times), saturated sodium bicarbonate (5 times) The solution is dried over Na2SO4 evaporated to dryness An oil is obtained which is dried to constant weight (30°-0.1 mm Hg)

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

实验步骤: 25 g of H-Ala-OMe, HCl and 66 g. of Boc-Ser-ONb are dissolved in 500 ml DMF. The product is cooled in an ice bath and 25 ml of NEM, 24 g of N-hydroxy benzotriazole are added with magnetic stirring and the pH is maintained at 6.5 or 7 by addition of NEM. The product is stirred for 18 hrs. at ambient temperature. After TLC monitoring, the medium is evaporated to 90% (0.1 mm Hg-35° C.). The oil obtained is dissolved in 1.500 ml of chloroform, the product is washed with a solution of saturated sodium chloride (twice), 5% sulfate/potassium bisulfate solution (3 times), saturated sodium bicarbonate (5 times). The solution is dried over Na2SO4 and evaporated to dryness. An oil is obtained which is dried to constant weight (30°-0.1 mm Hg). The product is cooled in an ice bath the pH is maintained at 6.5 or 7 by addition of NEM The product is stirred for 18 hrs at ambient temperature After TLC monitoring, the medium is evaporated to 90% (0.1 mm Hg-35° C.) The oil obtained the product is washed with a solution of saturated sodium chloride (twice), 5% sulfate/potassium bisulfate solution (3 times), saturated sodium bicarbonate (5 times) The solution is dried over Na2SO4 evaporated to dryness An oil is obtained which is dried to constant weight (30°-0.1 mm Hg)

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

实验步骤: Following General Procedure E and using (R/S)-3,5-difluoromandelic acid (as set forth in General Procedure H, step A) and L-alanine, methyl ester (Bachem) the title compound was synthesized.

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

实验步骤: Following General Procedure E and using (R/S)-3,5-difluoromandelic acid (as set forth in General Procedure H, step A) and L-alanine, methyl ester (Bachem) the title compound was synthesized.

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

实验步骤: Boc-(L)-Ala-(L)-Ala-OMe was prepared as follows. Boc-(L)-Ala-OH (2.06 g, 10.63 mmol) was dissolved in distilled dichloromethane (5 mL). To the resulting solution was added H2N-(L)-Ala-OMe (0.996 g, 9.67 mmol) in 5 mL of distilled dichloromethane. Dicyclohexylcarbodiimide (abbr. DCC; 2.19 g, 10.63 mmol) was dissolved in 3 mL distilled dichloromethane and added to the solution. Dicyclohexylurea (abbr. DCU) precipitation was noted immediately after DCC addition. Triethylamine (3 mL, 21.52 mmol) and additional distilled dichloromethane (4 mL) were added to the reaction mixture. The reaction proceeded for a total of three hours, when TLC analysis indicated consumption of H2N-(L)-Ala-OMe starting material and formation of a new component. DCU precipitation was promoted by storing the reaction at −20° C. The precipitate was filtered through a Buchner funnel and rinsed with cold dichloromethane. The combined filtrate and rinses were dried under vacuum and purified by Silica chromatography to yield dipeptide Boc-(L)-Ala-(L)-Ala-OMe (2.03 g, 7.14 mmol, 74%). 1H-NMR (chloroform-d) δ (ppm): 1.34 (d, J=14.1 Hz, 3H); 1.38 (d, J=14.3 Hz, 3H); 1.40 (s, 9H); 3.73 (s, 3H); 4.14 (s-broad, 1H); 4.55 (quintet, J=14.5 Hz, 1H); 4.97 (s-broad, 1H); 6.59 (s-broad, 1H). distilled dichloromethane added to the solution Dicyclohexylurea (abbr. DCU) precipitation after DCC addition were added to the reaction mixture proceeded for a total of three hours, when TLC analysis consumption of H2N-(L)-Ala-OMe starting material and formation of a new component DCU precipitation the reaction at −20° C The precipitate was filtered through a Buchner funnel rinsed with cold dichloromethane The combined filtrate and rinses were dried under vacuum purified by Silica chromatography

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

实验步骤: Boc-(L)-Ala-(L)-Ala-OMe was prepared as follows. Boc-(L)-Ala-OH (2.06 g, 10.63 mmol) was dissolved in distilled dichloromethane (5 mL). To the resulting solution was added H2N-(L)-Ala-OMe (0.996 g, 9.67 mmol) in 5 mL of distilled dichloromethane. Dicyclohexylcarbodiimide (abbr. DCC; 2.19 g, 10.63 mmol) was dissolved in 3 mL distilled dichloromethane and added to the solution. Dicyclohexylurea (abbr. DCU) precipitation was noted immediately after DCC addition. Triethylamine (3 mL, 21.52 mmol) and additional distilled dichloromethane (4 mL) were added to the reaction mixture. The reaction proceeded for a total of three hours, when TLC analysis indicated consumption of H2N-(L)-Ala-OMe starting material and formation of a new component. DCU precipitation was promoted by storing the reaction at −20° C. The precipitate was filtered through a Buchner funnel and rinsed with cold dichloromethane. The combined filtrate and rinses were dried under vacuum and purified by Silica chromatography to yield dipeptide Boc-(L)-Ala-(L)-Ala-OMe (2.03 g, 7.14 mmol, 74%). 1H-NMR (chloroform-d) δ (ppm): 1.34 (d, J=14.1 Hz, 3H); 1.38 (d, J=14.3 Hz, 3H); 1.40 (s, 9H); 3.73 (s, 3H); 4.14 (s-broad, 1H); 4.55 (quintet, J=14.5 Hz, 1H); 4.97 (s-broad, 1H); 6.59 (s-broad, 1H). distilled dichloromethane added to the solution Dicyclohexylurea (abbr. DCU) precipitation after DCC addition were added to the reaction mixture proceeded for a total of three hours, when TLC analysis consumption of H2N-(L)-Ala-OMe starting material and formation of a new component DCU precipitation the reaction at −20° C The precipitate was filtered through a Buchner funnel rinsed with cold dichloromethane The combined filtrate and rinses were dried under vacuum purified by Silica chromatography