反应详情

温度

-40 °C

To a solution of 1.83 g of Boc-L-phenylalanine in 15 ml of dimethylformamide is added 0.76 of N-methylmorpholine. The reaction mixture is cooled to -40° C. and 0.90 ml of isobutylchloroformate is added with stirring. The reaction mixture is stirred for 15 minutes at a temperature below -10° C. then 1.04 g of 3-amino-1-adamantanemethanol is added. The reaction mixture is stirred for 15 minutes at -20° C. then stored overnight at 5° C. The dimethylformamide is removed under reduced pressure and the residue is dissolved in methylene chloride and water. The methylene chloride phase is separated and washed twice with 35 ml of water, 3 times with 35 ml of a 0.5 M potassium bisulfate solution, and twice with 35 ml of water and then dried over magnesium sulfate. The solvent is removed under reduced pressure, and the residue is purified by chromatography on Whatman 10 micron silica gel eluting with a gradient of 1:1 hexane-chloroform to chloroform to give Boc-L-phenylalanyl-3-amino-adamantanemethanol. 2.0 Grams of this product is dissolved in 5 ml of a 6 N solution of hydrogen chloride in dioxane. The reaction mixture is allowed to stand for 20 minutes at room temperature then the solvent is removed under reduced pressure at 30° C., and the residue is stirred with diethyl ether to give the product as a solid. The solid product is collected by filtration and dried under reduced pressure to give L-phenylalanyl-3-amino-1-adamantanemethanol hydrochloride which is represented by the following structure ##STR70## When an equivalent quantity of L-phenylalanyl-3-amino-1-adamantanemethanol hydrochloride is substituted for the methyl L-phenylalanyl-3-amino-1-adamantanecarboxylate hydrochloride of Example 4 and the procedures detailed in Examples 4 through 9 substantially repeated there is obtained L-tyrosyl-D-methionyl-glycyl-L-phenylalanyl-3-amino-1-adamantanemethanol hydrochloride which is represented by the following formula ##STR71##

1. stirringThe reaction mixture is stirred for 15 minutes at a temperature below -10° C.
2. stirringThe reaction mixture is stirred for 15 minutes at -20° C.
3. customThe dimethylformamide is removed under reduced pressure
4. dissolutionthe residue is dissolved in methylene chloride
5. customThe methylene chloride phase is separated
6. washwashed twice with 35 ml of water, 3 times with 35 ml of a 0.5 M potassium bisulfate solution
7. dry with materialtwice with 35 ml of water and then dried over magnesium sulfate
8. customThe solvent is removed under reduced pressure
9. customthe residue is purified by chromatography on Whatman 10 micron silica gel eluting with a gradient of 1:1 hexane-chloroform to chloroform