反応 #46308

反応方程式

HCl

1-bromo-4-chlorobutane

6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-N,N-dimethyl-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxamide

magnesium methoxide

→

title compound

11-(3-Chloro-4-fluorobenzyl)-9-hydroxy-3,4,5,6,12,13-hexahydro-[1,4]oxazocino[3,4-a]-2,6-naphthyridine-1,8,10(11H)-trione

溶媒

DMSO

methanol

DMSO

反応条件

後処理

1. 1
   その他Methanol was exhaustively removed under vacuum over 45 minutes
2. 2
   温度The reaction mixture was heated at 100° C. for 3 hrs
3. 3
   その他The solid precipitated
4. 4
   ろ過was filtered
5. 5
   workup.DISSOLUTIONdissolved in DMSO
6. 6
   その他phase HPLC purification
7. 7
   その他Collection and lyophization of appropriate fractions

実験手順

A mixture of 6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-N,N-dimethyl-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxamide (0.80 g, 2.19 mmol; Example 1, step 9) and magnesium methoxide in methanol (10.6 mL, 6-10% methanol solution available from Aldrich) in DMSO (22 mL) was heated at 60° C. for 30 minutes. Methanol was exhaustively removed under vacuum over 45 minutes. The residual DMSO solution was treated with 1-bromo-4-chlorobutane (1.80 g, 10.50 mmol) and stirred at 60° C. under an atmosphere of nitrogen overnight. The reaction mixture was heated at 100° C. for 3 hrs. The reaction mixture was treated with dilute HCl. The solid precipitated was filtered, dissolved in DMSO, and subjected to reverse phase HPLC purification. Collection and lyophization of appropriate fractions provided the title compound.

出典