Browse Prior Art Database

Preparation of 5-ethyl 2-methyl 3-(benzyloxy)-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridine-2,5-dicarboxylate

IP.com Disclosure Number: IPCOM000238531D
Publication Date: 2014-Sep-03
Document File: 1 page(s) / 52K

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 81% of the total text.

Page 01 of 1

Preparation of 5-ethyl 2-methyl 3-(benzyloxy)-1-(2,2-dimethoxyethyl)-4-oxo-1,4-

dihydropyridine-2,5-dicarboxylate

Provided herein is a process for preparing methyl 5-ethyl 2-methyl 3-(benzyloxy)-1-(2,2- dimethoxyethyl)-4-oxo-1,4-dihydropyridine-2,5-dicarboxylate, referred herein as Compound I. The process is described in Example 1.

Compound I may be used for preparing (4R,12aS)-N-(2,4-difluorobenzyl)-7-hydroxy-4-methyl-6,8- dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide
and salts thereof.

Example 1:

Step A: Preparation of ethyl (E)-4-(benzyloxy)-2-(((2,2-dimethoxyethyl)amino)methylene)-3- oxobutanoate

Ethyl 4-(benzyloxy)-3-oxobutanoate (12 g) and 1,1-dimethoxy-N,N-dimethylmethanamine (7.08 g) were mixed together at RT for approximately 1.5h monitored by TLC (Hexane/EtOAc=3:1). As soon as no starting material was detected to the reaction mixture was added MeOH (36 ml) and 2,2- dimethoxyethan-1-amine (5.34 g). The obtained reaction mixture was stirred at RT for additional 2h followed by evaporation of MeOH to provide ethyl (E)-4-(benzyloxy)-2-(((2,2- dimethoxyethyl)amino)methylene)-3-oxobutanoate which was introduced to the next step without further purification.

Step B: Preparation of 5-ethyl 2-methyl 3-(benzyloxy)-1-(2,2-dimethoxyethyl)-4-oxo-1,4- dihydropyridine-2,5-dicarboxylate

Ethyl (E)-4-(benzyloxy)-2-(((2,2-dimethoxyethyl)amino)methylene)-3-oxobutanoate (1 g) was dissolved in MeOH (6 ml) and the obtained solutio...