2-(4-氨基苯基)丙-2-醇

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

实验步骤: The similar reaction as described in Example 40 by using 4-(N-benzyl-N-methylaminomethyl)-2-[N-(2,6-difluorobenzyl)-N-ethoxycarbonylamino]-5-[4-(3-methoxyureido)phenyl]thiophene-3-carboxylic acid (470 mg), diethyl cyanophosphate (167 μl), 4-(1-hydroxy-1-methylethyl)aniline (166 mg) and N-ethyldiisopropylamine (209 μl) gave a crude amide (422 mg). Furthermore, the similar reaction by using ethanol (25.5 ml) and sodium ethoxide (70 mg) gave the title compound (113 mg). The similar reaction gave a crude amide (422 mg) Furthermore, the similar reaction

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

实验步骤: The similar reaction as described in Example 40 by using 4-(N-benzyl-N-methylaminomethyl)-2-[N-(2,6-difluorobenzyl)-N-ethoxycarbonylamino]-5-[4-(3-methoxyureido)phenyl]thiophene-3-carboxylic acid (470 mg), diethyl cyanophosphate (167 μl), 4-(1-hydroxy-1-methylethyl)aniline (166 mg) and N-ethyldiisopropylamine (209 μl) gave a crude amide (422 mg). Furthermore, the similar reaction by using ethanol (25.5 ml) and sodium ethoxide (70 mg) gave the title compound (113 mg). The similar reaction gave a crude amide (422 mg) Furthermore, the similar reaction

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

实验步骤: The similar reaction as described in Example 40 by using 4-(N-benzyl-N-methylaminomethyl)-2-[N-(2,6-difluorobenzyl)-N-ethoxycarbonylamino]-5-[4-(3-methoxyureido)phenyl]thiophene-3-carboxylic acid (470 mg), diethyl cyanophosphate (167 μl), 4-(1-hydroxy-1-methylethyl)aniline (166 mg) and N-ethyldiisopropylamine (209 μl) gave a crude amide (422 mg). Furthermore, the similar reaction by using ethanol (25.5 ml) and sodium ethoxide (70 mg) gave the title compound (113 mg). The similar reaction gave a crude amide (422 mg) Furthermore, the similar reaction

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

实验步骤: To a 0° C. solution of acid 101 (0.32 g, 1.34 mmol) in DMF/DMSO (1:1, 20 mL) was added HATU (0.0.76 g, 2.01 mmol). The reaction was then stirred an additional 15 min at room temperature. The solution was cooled to 0° C. and amine 135 (0.30 g, 2.01 mmol) was added. The reaction was then stirred at rt overnight. The DMF was concentrated in vacuo and water was added to the reaction. The aqueous layer was extracted with EtOAc The ethyl acetate layer was then washed again with water and the organic layer was concentrated in vacuo. The product was purified by flash chromatography on silica gel eluting with EtOAc/hexanes and EtOAc/MeOH to yield 402 as a pure light brown semi solid (0.086 g, 17.5%). MS (APCI): m/z 372.2 [M−H]+ Anal. Calcd. For C18H21N5O4. 0.35 EtOAc: C, 57.93; H, 5.96; N, 17.41. Found C, 58.36; H, 6.14; N, 16.96. The solution was cooled to 0° C. The reaction was then stirred at rt overnight The DMF was concentrated in vacuo and water was added to the reaction The aqueous layer was extracted with EtOAc The ethyl acetate layer was then washed again with water the organic layer was concentrated in vacuo The product was purified by flash chromatography on silica gel eluting with EtOAc/hexanes and EtOAc/MeOH

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a −78° C. solution of compound 134 (1 g, 3.95 mmol) in ether (20 mL) was added sec-BuLi (1.4 M in hexanes, 0.62 g, 9.67 mmol). The resulting solution was stirred for 30 min at −78° C., followed by addition of acetone (0.91 g, 15.81 mmol) dropwise at −78° C. The reaction mixture was warmed to room temperature overnight. The reaction mixture was partitioned between water and ether and the layers were separated. The aqueous layer was re-extracted with ether. The ether layers were the combined and concentrated in vacuo to yield crude 135 (0.33 g, 55.9%) which was used in the next step without further purification. The reaction mixture was warmed to room temperature overnight The reaction mixture was partitioned between water and ether the layers were separated The aqueous layer was re-extracted with ether concentrated in vacuo

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

实验步骤: To a 0° C. solution of acid 101 (0.32 g, 1.34 mmol) in DMF/DMSO (1:1, 20 mL) was added HATU (0.0.76 g, 2.01 mmol). The reaction was then stirred an additional 15 min at room temperature. The solution was cooled to 0° C. and amine 135 (0.30 g, 2.01 mmol) was added. The reaction was then stirred at rt overnight. The DMF was concentrated in vacuo and water was added to the reaction. The aqueous layer was extracted with EtOAc The ethyl acetate layer was then washed again with water and the organic layer was concentrated in vacuo. The product was purified by flash chromatography on silica gel eluting with EtOAc/hexanes and EtOAc/MeOH to yield 402 as a pure light brown semi solid (0.086 g, 17.5%). MS (APCI): m/z 372.2 [M−H]+ Anal. Calcd. For C18H21N5O4. 0.35 EtOAc: C, 57.93; H, 5.96; N, 17.41. Found C, 58.36; H, 6.14; N, 16.96. The solution was cooled to 0° C. The reaction was then stirred at rt overnight The DMF was concentrated in vacuo and water was added to the reaction The aqueous layer was extracted with EtOAc The ethyl acetate layer was then washed again with water the organic layer was concentrated in vacuo The product was purified by flash chromatography on silica gel eluting with EtOAc/hexanes and EtOAc/MeOH

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a −78° C. solution of compound 134 (1 g, 3.95 mmol) in ether (20 mL) was added sec-BuLi (1.4 M in hexanes, 0.62 g, 9.67 mmol). The resulting solution was stirred for 30 min at −78° C., followed by addition of acetone (0.91 g, 15.81 mmol) dropwise at −78° C. The reaction mixture was warmed to room temperature overnight. The reaction mixture was partitioned between water and ether and the layers were separated. The aqueous layer was re-extracted with ether. The ether layers were the combined and concentrated in vacuo to yield crude 135 (0.33 g, 55.9%) which was used in the next step without further purification. The reaction mixture was warmed to room temperature overnight The reaction mixture was partitioned between water and ether the layers were separated The aqueous layer was re-extracted with ether concentrated in vacuo

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

实验步骤: To a 0° C. solution of acid 101 (0.32 g, 1.34 mmol) in DMF/DMSO (1:1, 20 mL) was added HATU (0.0.76 g, 2.01 mmol). The reaction was then stirred an additional 15 min at room temperature. The solution was cooled to 0° C. and amine 135 (0.30 g, 2.01 mmol) was added. The reaction was then stirred at rt overnight. The DMF was concentrated in vacuo and water was added to the reaction. The aqueous layer was extracted with EtOAc The ethyl acetate layer was then washed again with water and the organic layer was concentrated in vacuo. The product was purified by flash chromatography on silica gel eluting with EtOAc/hexanes and EtOAc/MeOH to yield 402 as a pure light brown semi solid (0.086 g, 17.5%). MS (APCI): m/z 372.2 [M−H]+ Anal. Calcd. For C18H21N5O4. 0.35 EtOAc: C, 57.93; H, 5.96; N, 17.41. Found C, 58.36; H, 6.14; N, 16.96. The solution was cooled to 0° C. The reaction was then stirred at rt overnight The DMF was concentrated in vacuo and water was added to the reaction The aqueous layer was extracted with EtOAc The ethyl acetate layer was then washed again with water the organic layer was concentrated in vacuo The product was purified by flash chromatography on silica gel eluting with EtOAc/hexanes and EtOAc/MeOH

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a −78° C. solution of compound 134 (1 g, 3.95 mmol) in ether (20 mL) was added sec-BuLi (1.4 M in hexanes, 0.62 g, 9.67 mmol). The resulting solution was stirred for 30 min at −78° C., followed by addition of acetone (0.91 g, 15.81 mmol) dropwise at −78° C. The reaction mixture was warmed to room temperature overnight. The reaction mixture was partitioned between water and ether and the layers were separated. The aqueous layer was re-extracted with ether. The ether layers were the combined and concentrated in vacuo to yield crude 135 (0.33 g, 55.9%) which was used in the next step without further purification. The reaction mixture was warmed to room temperature overnight The reaction mixture was partitioned between water and ether the layers were separated The aqueous layer was re-extracted with ether concentrated in vacuo

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a −78° C. solution of compound 134 (1 g, 3.95 mmol) in ether (20 mL) was added sec-BuLi (1.4 M in hexanes, 0.62 g, 9.67 mmol). The resulting solution was stirred for 30 min at −78° C., followed by addition of acetone (0.91 g, 15.81 mmol) dropwise at −78° C. The reaction mixture was warmed to room temperature overnight. The reaction mixture was partitioned between water and ether and the layers were separated. The aqueous layer was re-extracted with ether. The ether layers were the combined and concentrated in vacuo to yield crude 135 (0.33 g, 55.9%) which was used in the next step without further purification. The reaction mixture was warmed to room temperature overnight The reaction mixture was partitioned between water and ether the layers were separated The aqueous layer was re-extracted with ether concentrated in vacuo

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a −78° C. solution of compound 134 (1 g, 3.95 mmol) in ether (20 mL) was added sec-BuLi (1.4 M in hexanes, 0.62 g, 9.67 mmol). The resulting solution was stirred for 30 min at −78° C., followed by addition of acetone (0.91 g, 15.81 mmol) dropwise at −78° C. The reaction mixture was warmed to room temperature overnight. The reaction mixture was partitioned between water and ether and the layers were separated. The aqueous layer was re-extracted with ether. The ether layers were the combined and concentrated in vacuo to yield crude 135 (0.33 g, 55.9%) which was used in the next step without further purification. The reaction mixture was warmed to room temperature overnight The reaction mixture was partitioned between water and ether the layers were separated The aqueous layer was re-extracted with ether concentrated in vacuo

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

实验步骤: To a 0° C. solution of acid 101 (0.32 g, 1.34 mmol) in DMF/DMSO (1:1, 20 mL) was added HATU (0.0.76 g, 2.01 mmol). The reaction was then stirred an additional 15 min at room temperature. The solution was cooled to 0° C. and amine 135 (0.30 g, 2.01 mmol) was added. The reaction was then stirred at rt overnight. The DMF was concentrated in vacuo and water was added to the reaction. The aqueous layer was extracted with EtOAc The ethyl acetate layer was then washed again with water and the organic layer was concentrated in vacuo. The product was purified by flash chromatography on silica gel eluting with EtOAc/hexanes and EtOAc/MeOH to yield 402 as a pure light brown semi solid (0.086 g, 17.5%). MS (APCI): m/z 372.2 [M−H]+ Anal. Calcd. For C18H21N5O4.0.35 EtOAc: C, 57.93; H, 5.96; N, 17.41; Found C, 58.36; H, 6.14; N, 16.96. The solution was cooled to 0° C. The reaction was then stirred at rt overnight The DMF was concentrated in vacuo and water was added to the reaction The aqueous layer was extracted with EtOAc The ethyl acetate layer was then washed again with water the organic layer was concentrated in vacuo The product was purified by flash chromatography on silica gel eluting with EtOAc/hexanes and EtOAc/MeOH