4-Toluenesulfonyl chloride → [(4R/S)-3-Fluoro-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl]methyl 4-methylbenzenesulfonate

HRID 15120

Reaktionsgleichung

Reaktionsgleichung von HRID 15120
[F:1][C:2]1[CH:3]=[N:4][C:5]2[CH:6]=[CH:7][C:8](=[O:17])[N:9]3[CH2:13][C:12]([OH:16])([CH2:14][OH:15])[C:11]=1[C:10]=23.FC1C=NC2C=CC(=O)N3CC(=C)C=1C=23.C(N(CC)CC)C.[C:40]1([CH3:50])[CH:45]=[CH:44][C:43]([S:46](Cl)(=[O:48])=[O:47])=[CH:42][CH:41]=1.C([Sn](=O)CCCC)CCC>ClCCl.O1CCCC1.CN(C)C=O.O>[CH3:50][C:40]1[CH:45]=[CH:44][C:43]([S:46]([O:15][CH2:14][C:12]2([OH:16])[C:11]3=[C:2]([F:1])[CH:3]=[N:4][C:5]4[CH:6]=[CH:7][C:8](=[O:17])[N:9]([C:10]=43)[CH2:13]2)(=[O:48])=[O:47])=[CH:42][CH:41]=1

Komponenten

8

Edukt 5

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 61221Dibutyltin oxideHCID 23634273(4R/S)-3-fluoro-4-hydroxy-4-(hydroxymethyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-oneHCID 675275493-Fluoro-4-methylidene-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one

Produkt 1

HCID 131728163[(4R/S)-3-Fluoro-4-hydroxy-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl]methyl 4-methylbenzenesulfonate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 86642945dichloromethane tetrahydrofuran DMFLösungsmittel

Versuchsvorschrift

A mixture of (4R/S)-3-fluoro-4-hydroxy-4-(hydroxymethyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one (553 mg, 2.3 mmol) (racemic material, prepared from 3-fluoro-4-methylidene-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one using AD mix alpha/beta in a similar manner to Example 1(e) Method A) in dichloromethane/tetrahydrofuran/N,N-dimethylformamide (19 ml19 ml/2 ml) was treated with triethylamine (0.5 ml, 3.5 mmol), para-toluenesulphonyl chloride (446 mg, 2.3 mmol) and dibutyltin oxide (29 mg, 0.1 mmol) and stirred at room temperature overnight. Water was then added, the organic phase was separated and washed with saturated aqueous sodium bicarbonate, separated, dried over magnesium sulphate and evaporated under vacuum. The residue was chromatographed on silica eluting with 0-100% ethyl acetate in dichloromethane then 0-10% methanol in ethyl acetate affording a white solid (321 mg, 35%).

Aufarbeitung

  1. customthe organic phase was separated
  2. washwashed with saturated aqueous sodium bicarbonate
  3. customseparated
  4. dry with materialdried over magnesium sulphate
  5. customevaporated under vacuum
  6. customThe residue was chromatographed on silica eluting with 0-100% ethyl acetate in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-90c35ecce929460ca5f37a3bf5782e19
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07732460B2

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