The invention relates to a preparation method of entcartide
hydrochloride. The preparation method comprises the following steps: step 1, synthesizing a D-
acetylcysteine-L-Boc-
cysteine methyl ester disulfide-D-
alanine tripeptide compound through a
liquid phase synthesis method; step 2, synthesizing a D-Pbf-
arginine amide-D-
alanine-D-Pbf-
arginine-D-Pbf-
arginine-D-Pbf-arginine pentapeptide compound by virtue of a
liquid phase synthesis method, and synthesizing a D-Pbf-arginine pentapeptide compound by virtue of a
liquid phase synthesis method; step 3, carrying out liquid phase condensation on the D-
acetylcysteine-L-Boc-
cysteine methyl ester disulfide-D-
alanine tripeptide compound and the D-Pbf-arginine
amide-D-alanine-D-Pbf-arginine-D-Pbf-arginine pentapeptide compound, so as to obtain an Itecartide precursor, and carrying out liquid phase condensation on the Itecartide precursor and the D-Pbf-arginine pentapeptide compound, so as to obtain the Itecartide. And step 4, carrying out deprotection,
hydrolysis and salt conversion on the itecartide precursor to obtain the itecartide
hydrochloride. The preparation method disclosed by the invention is simple to operate, low in cost, high in directional conversion rate, environment-friendly and high in product yield and purity.