1-Bromo-2-Chloroethane → 9-(3-Chloro-4-fluorobenzyl)-7-hydroxy-3,4,10,11-tetrahydro[1,4]oxazino[3,4-a]-2,6-naphthyridine-1,6,8(9H)-trione

HRID 2066584

反応式

HRID 2066584 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:12]([C:16](N(C)C)=[O:17])=[N:11][C:10]([OH:21])=[C:9]([OH:22])[C:8]=2[C:7]1=[O:23].C[O-:29].[Mg+2].C[O-].Br[CH2:34][CH2:35]Cl>CO.CS(C)=O.C(OCC)(=O)C.Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([OH:22])[C:10](=[O:21])[N:11]3[CH2:35][CH2:34][O:29][C:16](=[O:17])[C:12]3=2)[C:7]1=[O:23]

参加物

8

反応物 3

HCID 78491-Bromo-2-ChloroethaneHCID 164537Methanol, magnesium salt (2:1)HCID 178484497HCID 178484497、化合物

生成物 1

HCID 593446999-(3-Chloro-4-fluorobenzyl)-7-hydroxy-3,4,10,11-tetrahydro[1,4]oxazino[3,4-a]-2,6-naphthyridine-1,6,8(9H)-trione

試薬・触媒・溶媒 4

HCID 313Hydrochloric Acid溶媒HCID 679Dimethyl Sulfoxide溶媒2 回HCID 887Methanol溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

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 (0.15 g, 0.39 mmol; Example 1, Step 9) and magnesium methoxide in methanol (2 mL, 6-10% methanol solution available from Aldrich) in DMSO (4 mL) was heated at 60° C. for 30 minutes. Methanol was exhaustively removed under vacuum over 45 minutes. The resultant DMSO solution was treated with 1-bromo-2-chloroethane (0.28 g, 1.97 mmol) and stirred at 60° C. under an atmosphere of nitrogen overnight. The reaction mixture was diluted with ethyl acetate and dilute hydrochloric acid. The organic extract was washed with aqueous sodium sulfite, brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by reverse phase high pressure liquid chromatography. Collection and lyophilization of appropriate fractions provided the title compound, which was recrystallized from a mixture of ethyl acetate and hexane

後処理

  1. customMethanol was exhaustively removed under vacuum over 45 minutes
  2. extractionThe organic extract
  3. washwas washed with aqueous sodium sulfite, brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by reverse phase high pressure liquid chromatography
  8. customCollection and lyophilization of appropriate fractions

出典と根拠

ORDレコード
ord-facb6da1b0fb43f88e0a3ece8ce21271
出典データセット
uspto-grants-2012_10
特許番号
US08293731B2

関連ノート

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