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1,4-anhydro-2-O-(2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5,8-dichloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-deoxy-L-threo-pentitol → 1,4-anhydro-3-deoxy-2-O-{5,8-dichloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl}-L-threo-pentitol

HRID 577496
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Reaktionsgleichung

Reaktionsgleichung von HRID 577496
C([O:8][C:9]1[C:14]([CH2:15][N:16]2[CH2:25][CH2:24][C:23]3[C:18](=[C:19]([Cl:35])[C:20]([O:27][C@@H:28]4[CH2:32][C@H:31]([CH2:33][OH:34])[O:30][CH2:29]4)=[CH:21][C:22]=3[Cl:26])[C:17]2=[O:36])=[C:13]([CH3:37])[CH:12]=[C:11]([CH3:38])[N:10]=1)C1C=CC=CC=1>FC(F)(F)C(O)=O>[Cl:26][C:22]1[CH:21]=[C:20]([O:27][C@@H:28]2[CH2:32][C@H:31]([CH2:33][OH:34])[O:30][CH2:29]2)[C:19]([Cl:35])=[C:18]2[C:23]=1[CH2:24][CH2:25][N:16]([CH2:15][C:14]1[C:9](=[O:8])[NH:10][C:11]([CH3:38])=[CH:12][C:13]=1[CH3:37])[C:17]2=[O:36]
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Komponenten

3

Edukt 1

HCID 867237211,4-anhydro-2-O-(2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5,8-dichloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-deoxy-L-threo-pentitol

Produkt 1

HCID 867237221,4-anhydro-3-deoxy-2-O-{5,8-dichloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl}-L-threo-pentitolAusbeute 40 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6422Trifluoroacetic acidLösungsmittel

Versuchsvorschrift

A solution of 1,4-anhydro-2-O-(2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5,8-dichloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-deoxy-L-threo-pentitol (296o, 36 mg, 0.065 mmol) in trifluoroacetic acid (2 mL) was stirred at room temperature for three hours. The volatiles were removed under vacuum, and the residue partitioned between ethyl acetate (20 mL) and saturated aqueous sodium bicarbonate (20 mL). The aqueous layer was back-extracted with ethyl acetate (2×20 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (eluting with a gradient of 0-10% methanol in ethyl acetate) to yield 1,4-anhydro-3-deoxy-2-O-{5,8-dichloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl}-L-threo-pentitol (Example 296, 12 mg, 40% yield), as a solid, after lyophilization. 1H NMR (400 MHz, methanol-d4) δ 7.14 (s, 1H), 6.00 (s, 1H), 4.93-5.02 (m, 1H), 4.64 (s, 2H), 3.95-4.06 (m, 2H), 3.85 (dd, J=10.39, 4.28 Hz, 1H), 3.56-3.64 (m, 1H), 3.49-3.55 (m, 1H), 3.38 (t, J=6.17 Hz, 2H), 2.80 (t, J=6.24 Hz, 2H), 2.36 (ddd, J=14.09, 7.79, 6.60 Hz, 1H), 2.18 (s, 3H), 2.14 (s, 3H), 1.84 (dd, J=13.94, 5.50 Hz, 1H).

Aufarbeitung

  1. customThe volatiles were removed under vacuum
  2. customthe residue partitioned between ethyl acetate (20 mL) and saturated aqueous sodium bicarbonate (20 mL)
  3. extractionThe aqueous layer was back-extracted with ethyl acetate (2×20 mL)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. concentrationconcentrated
  6. custompurified by silica gel chromatography (
  7. washeluting with a gradient of 0-10% methanol in ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-e31c9a3bb246460c879f9b96bc1a3e7f
Quelldatensatz
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09040515B2

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