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Ethyl Acetate → [5-({3-fluoro-2-(2-fluoropyridin-3-yl)-4-[(methylamino)methyl]-1H-pyrrol-1-yl}sulfonyl)-2-furyl]methyl acetate fumarate

HRID 1426821
ノート
印刷プレビュー

反応式

HRID 1426821 の反応式
[F:1][C:2]1[C:3]([CH2:24][N:25]([CH3:33])C(=O)OC(C)(C)C)=[CH:4][N:5]([S:14]([C:17]2[O:18][C:19]([CH2:22][OH:23])=[CH:20][CH:21]=2)(=[O:16])=[O:15])[C:6]=1[C:7]1[C:8]([F:13])=[N:9][CH:10]=[CH:11][CH:12]=1.[C:34]([O:37]CC)(=[O:36])[CH3:35].Cl.[C:41]([O:44]CC)(=[O:43])[CH3:42]>CC(O)C>[C:41]([OH:44])(=[O:43])/[CH:42]=[CH:35]/[C:34]([OH:37])=[O:36].[C:34]([O:23][CH2:22][C:19]1[O:18][C:17]([S:14]([N:5]2[CH:4]=[C:3]([CH2:24][NH:25][CH3:33])[C:2]([F:1])=[C:6]2[C:7]2[C:8]([F:13])=[N:9][CH:10]=[CH:11][CH:12]=2)(=[O:16])=[O:15])=[CH:21][CH:20]=1)(=[O:36])[CH3:35]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 8857Ethyl AcetateHCID 21866389Hydrogen chloride-ethyl acetateHCID 67398835tert-butyl [(4-fluoro-5-(2-fluoropyridin-3-yl)-1-{[5-(hydroxymethyl)-2-furyl]sulfonyl}-1H-pyrrol-3-yl)methyl]methylcarbamate

生成物 1

HCID 69036245[5-({3-fluoro-2-(2-fluoropyridin-3-yl)-4-[(methylamino)methyl]-1H-pyrrol-1-yl}sulfonyl)-2-furyl]methyl acetate fumarate

試薬・触媒・溶媒 1

HCID 3776
Isopropanol
溶媒

実験手順

To a solution of tert-butyl [(4-fluoro-5-(2-fluoropyridin-3-yl)-1-{[5-(hydroxymethyl)-2-furyl]sulfonyl}-1H-pyrrol-3-yl)methyl]methylcarbamate (223 mg) in ethyl acetate (2 mL) and 2-propanol (1 mL) was added 4 mol/L hydrogen chloride-ethyl acetate solution (3 mL), and the mixture was stirred at room temperature for 1 hr. The solvent was concentrated under reduced pressure, the residue was diluted with ethyl acetate, and washed with saturated aqueous sodium hydrogen carbonate solution. The separated aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent:hexane-ethyl acetate=2:3→ethyl acetate) to give the title compound as a free base (basic TLC:Rf=0.22 (hexane:ethyl acetate=1:1)) (yield 42.2 mg). A solution of the obtained free base (42.2 mg) in ethyl acetate (2 mL) was added dropwise to a solution of fumaric acid (11.5 mg) in ethanol (2 mL) and the mixture was concentrated under reduced pressure. The residue was recrystallized from a mixed solvent of ethyl acetate-ethanol to give the title compound as a white solid (yield 37.4 mg, 23%).

後処理

  1. concentrationThe solvent was concentrated under reduced pressure
  2. additionthe residue was diluted with ethyl acetate
  3. washwashed with saturated aqueous sodium hydrogen carbonate solution
  4. extractionThe separated aqueous layer was extracted again with ethyl acetate
  5. washThe combined organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by basic silica gel column chromatography (eluent:hexane-ethyl acetate=2:3→ethyl acetate)

出典と根拠

ORDレコード
ord-7e7f846a733449ea857d5029016ba4c5
出典データセット
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08933105B2

反応ノート

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