新产品编号:1631551

Chemical Name: 1-(2-Methylalanyl-D-tryptophyl)-3-(2-pyridylmethyl)piperidine-3(S)-carboxylic acid ethyl ester
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线:Protection of ethyl piperidine-3-carboxylate (I) with di tert-butyl dicarbonate gave carbamate (II),which was alkylated with 4-(bromomethyl)thiazole (III) in the presence of potassium hexamethyldisilazide to afford racemic (IV).Acid deprotection of the Boc group of (IV) yielded amine (V).This was resolved by coupling with (R)-O-acetyl mandelic acid (VI),followed by chromatographic separation of the diastereoisomers.Then,acid hydrolysis of the desired isomer (VII) provided the (S)-piperidine (VIII).Subsequent coupling of (VIII) with N-Boc-D-tryptophan (IX) in the presence of EDC and HOBt gave amide (X).After Boc deprotection of (X),the resulting amine (XI) was coupled with N-Boc-2-aminoisobutyric acid (XII) to produce (XIII).Finally,acid removal of the Boc group of (XIII) furnished the title compound.

合成路线:Protection of ethyl piperidine-3-carboxylate (I) with di tert-butyl dicarbonate gave carbamate (II),which was alkylated with 2-(chloromethyl)pyridine chloride (III) in the presence of potassium hexamethyldisilazide to afford racemic (IV).Acid deprotection of the Boc group of (IV) yielded amine (V).This was resolved by coupling with (R)-O-acetyl mandelic acid (VI),followed by chromatographic separation of the diastereoisomers.Then,acid hydrolysis of the desired isomer (VII) provided the (S)-piperidine (VIII).Subsequent coupling of (VIII) with N-Boc-D-tryptophan (IX) in the presence of EDC and HOBt gave amide (X).After Boc deprotection of (X),the resulting amine (XI) was coupled with N-Boc-2-aminoisobutyric acid (XII) to produce (XIII).Finally,acid removal of the Boc group of (XIII) furnished the title compound.