Methanol, magnesium salt (2:1) → 9-(3-Chloro-4-fluorobenzyl)-7-hydroxy-3,4,10,11-tetrahydro-2H-pyrazino[2,1-a]-2,6-naphthyridine-1,6,8(9H)-trione

HRID 2426455노트

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HRID 2426455 반응식
[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:18]([CH3:20])C)=[O:17])=[N:11][C:10]([OH:21])=[C:9]([OH:22])[C:8]=2[C:7]1=[O:23].C[O-].[Mg+2].C[O-].Br[CH2:34]CNC(=O)OCCCC>CO.CS(C)=O.C(OCC)(=O)C>[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[CH2:34][CH2:20][NH:18][C:16](=[O:17])[C:12]3=2)[C:7]1=[O:23]

참가 물질

7

반응물 3

HCID 164537Methanol, magnesium salt (2:1)HCID 23033729Butyl (2-bromoethyl)carbamateHCID 178484497HCID 178484497, 화합물

생성물 1

HCID 593447509-(3-Chloro-4-fluorobenzyl)-7-hydroxy-3,4,10,11-tetrahydro-2H-pyrazino[2,1-a]-2,6-naphthyridine-1,6,8(9H)-trione

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매2회HCID 887Methanol용매HCID 8857Ethyl Acetate용매

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온도
60 °C

실험 절차

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 (1.00 g, 2.63 mmol; Example 1, Step 9) and magnesium methoxide in methanol (13.1 mL, 6-10% methanol solution available from Aldrich) in DMSO (26 mL) was heated at 60° C. for one hour. Methanol was exhaustively removed under vacuum over 45 minutes. The resulting DMSO solution was treated with tort-butyl (2-bromoethyl)carbamate (2.94 g, 13.13 mmol) and stirred at 60° C. under an atmosphere of nitrogen for one hour. The reaction mixture was diluted with ethyl acetate and washed successively with 10% sodium thiosulfate and brine. The organic extract was 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.

후처리

  1. customMethanol was exhaustively removed under vacuum over 45 minutes
  2. washwashed successively with 10% sodium thiosulfate and brine
  3. extractionThe organic extract
  4. dry with materialwas dried 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

출처 및 근거

ORD 기록
ord-9efdab718ca7455b8ee9877182461b31
출처 데이터셋
uspto-grants-2011_06
특허 번호
US07968564B2

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