乙基 4-(2-氨基苯氧基)丁酸乙酯

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

实验步骤: To a solution of (4) (2.60 g., 11 mM) and 11-bromoundecanoic acid (2.65 g., 10 mM) in anhydrous methylene chloride (90 mL) is added 4-(dimethylamino)pyridine (1.22 g., 10 mM) followed by N,N'-dicyclohexylcarbodiimide (2.3 g., 11 mM) (4×5 mL of methylenechloride rinses). Precipitation of dicyclohexylurea (DCU) begins within 4 minutes. When TLC analysis indicates the reaction is complete, the mixture is filtered, the filtrate concentrated in vacuo and the residue extracted with ether. The combined ether extracts are washed 1× with 1N hydrochloric acid, 1× saturated sodium chloride solution, dried (Na2SO4) and concentrated to a residue which is stirred, filtered, and concentrated alternately with ether and methylene chloride until all DCU is removed. Concentration of the final solution yields the title product (32) (2.35 g.) as an oil that goes readily to a waxy solid. Precipitation of dicyclohexylurea (DCU) the mixture is filtered the filtrate concentrated in vacuo the residue extracted with ether The combined ether extracts are washed 1× with 1N hydrochloric acid, 1× saturated sodium chloride solution dried (Na2SO4) concentrated to a residue which filtered concentrated alternately with ether and methylene chloride until all DCU is removed

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

实验步骤: To a stirred, ice-cold solution of 0.89 g (4.0 mM) amine (4) and dried triethylamine (1.2 mL) in dry ether (40 mL) is added dropwise over ca. 4 minutes a solution of acid chloride (7) (1.04 g, 4.6 mM) in 20 mL of dry ether. The resultant mixture is allowed to stir cold for 20 minutes, and then at room temperature overnight. After filtering off the triethylamine hydrochloride, the ether filtrate is concentrated in vacuo and the residue chromatographed on an 82 g silica gel column using 20% ethyl acetate/hexane as eluant to give 1.49 g (85%) of (8) as a waxy solid. at room temperature overnight After filtering off the triethylamine hydrochloride the ether filtrate is concentrated in vacuo the residue chromatographed on an 82 g silica gel column

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

实验步骤: A solution of (3) (1.27 g, 5.0 mM) in 15 mL ethyl acetate containing 200 mg of 5% palladium on carbon is reacted in a hydrogen atmosphere (40 psig.) at room temperature until hydrogen uptake ceases. The mixture is then filtered and concentrated in vacuo to yield 1.0+ g of (4) as an oil/low melting solid. The mixture is then filtered concentrated in vacuo

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

实验步骤: A solution of (3) (1.27 g, 5.0 mM) in 15 mL ethyl acetate containing 200 mg of 5% palladium on carbon is reacted in a hydrogen atmosphere (40 psig.) at room temperature until hydrogen uptake ceases. The mixture is then filtered and concentrated in vacuo to yield 1.0+ g of (4) as an oil/low melting solid. The mixture is then filtered 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 solution of (4) (0.25 g, 1.14 mM) and (6) (0.274 g, 1.0 mM) in dry methylene chloride (10 mL) at room temperature was added 4-dimethylamino-pyridine (0.122 g, 1.0 mM) followed within one minute by a solution of N,N'-dicyclohexylcarbodiimide (0.22 g, 1.06 mM) in methylene chloride (1 mL), 3×1 mL rinses with methylene chloride. After 2 days, the filtered mixture was concentrated in vacuo and the residue flash chromatographed on silica gel using 15-20% ethyl acetate in hexane as eluant to give product 7 (0.22 g) as an oil that solidified readily in a short time. the filtered mixture was concentrated in vacuo the residue flash chromatographed on silica gel using 15-20% ethyl acetate in hexane as eluant

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

实验步骤: 0.38 g of compound 74 was obtained in a similar manner to those described in the Examples 1 and 2 using 0.51 g of ethyl 4-(2-aminophenoxy)butyrate and 0.45 g of 3-[1-(2,4'-dimethylbenzhydryl)indol-5-yl]isocrotonic acid obtained according to the procedures described in the Reference Examples 1-4. obtained

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

实验步骤: 0.38 g of compound 74 was obtained in a similar manner to those described in the Examples 1 and 2 using 0.51 g of ethyl 4-(2-aminophenoxy)butyrate and 0.45 g of 3-[1-(2,4'-dimethylbenzhydryl)indol-5-yl]isocrotonic acid obtained according to the procedures described in the Reference Examples 1-4. obtained

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

实验步骤: 0.38 g of compound 74 was obtained in a similar manner to those described in the Examples 1 and 2 using 0.51 g of ethyl 4-(2-aminophenoxy)butyrate and 0.45 g of 3-[1-(2,4'-dimethylbenzhydryl)indol-5-yl]isocrotonic acid obtained according to the procedures described in the Reference Examples 1-4. obtained

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

实验步骤: 0.20 g of compound 73 was obtained in a similar manner to those described in the Examples 1 and 2 using 0.41 g of ethyl 4-(2-aminophenoxy)butyrate and 0.36 g of 3-[1-(2,3'-dimethylbenzhydryl)indol-5yl]isocrotonic acid obtained according to the procedures described in the Reference Examples 1-4. obtained

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

实验步骤: 0.55 g of amorphous compound 72 was obtained in a similar manner to those described in the Examples 1 and 2 using 0.63 g of ethyl 4-(2-aminophenoxy)butyrate and 0.56 g of 3-[1-[2,2'-dimethylbenzhydryl)indol-5-yl] isocrotonic acid obtained according to the procedures described in the Reference Examples 1-4. obtained

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

实验步骤: 217 mg of compound 61 was obtained in a similar manner to those described in the Examples 1 and 2 using 438 mg of ethyl 4-(2-aminophenoxy)butyrate and 429 mg of 3-[1-(4,4'-dichlorobenzhydryl)indol-5-yl]isocrotonic acid obtained according to the procedures described in the Reference Examples 1-4. obtained

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

实验步骤: 0.31 g of compound 59 was obtained in a similar manner to those described in the Examples 1 and 2 using 1.11 g of ethyl 4-(2-aminophenoxy)butyrate and 1.0 g of 3-[1-(4,4'-difluorobenzhydryl)indol-5-yl]isocrotonic acid obtained according to the procedures described in the Reference Examples 1-4. obtained