Water → Dodecyl-2-((1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)carbamoyl)benzoate

HRID 241530

Reaktionsgleichung

Reaktionsgleichung von HRID 241530
[CH:1]1[C:7]([NH2:8])=[N:6][C:4](=[O:5])[N:3]([C@@H:9]2[O:13][C@H:12]([CH2:14][OH:15])[C@@H:11]([OH:16])[C:10]2([F:18])[F:17])[CH:2]=1.Cl.[CH2:20]([O:32][C:33]([C:35]1[CH:43]=[CH:42][CH:41]=[CH:40][C:36]=1[C:37](O)=[O:38])=[O:34])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.O>CN(C)C1C=CN=CC=1.CN(C)C=O>[CH2:20]([O:32][C:33](=[O:34])[C:35]1[CH:43]=[CH:42][CH:41]=[CH:40][C:36]=1[C:37](=[O:38])[NH:8][C:7]1[CH:1]=[CH:2][N:3]([C@H:9]2[C:10]([F:17])([F:18])[C@H:11]([OH:16])[C@@H:12]([CH2:14][OH:15])[O:13]2)[C:4](=[O:5])[N:6]=1)[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]

Komponenten

7

Edukt 4

HCID 962WaterHCID 60749Gemcitabine HydrochlorideHCID 88948Dodecyl phthalateHCID 2724699PyBOP

Produkt 1

HCID 60201196Dodecyl-2-((1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)carbamoyl)benzoateAusbeute 26,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Gemcitabine hydrochloride (0.7 g, 2.34 mmol), 2-(dodecyloxycarbonyl)benzoic acid (1.02 g, 3.04 mmol), (Benzotriazol-1-yl-oxy)tripyrrolidinylphosphonium hexafluorophosphate (1.34 g, 2.57 mmol), and 4-dimethylaminopyridine (428 mg, 3.51 mmol) were dissolved in N,N-dimethylformamide (10 mL) and stirred overnight at room temperature. The reaction mixture was poured into water, and then extracted three times with ethyl acetate. The isolated organic phase was dried with anhydrous Na2SO4. The solvent was removed by vaporizing under reduced pressure. The residue was purified by silica column chromatography (developing agent: dichloromethane/methanol=30/1) to produce 362.5 mg of Dodecyl-2-((1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)carbamoyl)benzoate. LC purity 98% (UV254). LC-MS m/z 580 [M+H]+ (molecular formula: C29H39F2N3O7, molecule weight: 579). The structure and characterization data of the compound were shown in Table 1.

Aufarbeitung

  1. extractionextracted three times with ethyl acetate
  2. dry with materialThe isolated organic phase was dried with anhydrous Na2SO4
  3. customThe solvent was removed
  4. customThe residue was purified by silica column chromatography (developing agent: dichloromethane/methanol=30/1)

Quellen und Nachweise

ORD-Eintrag
ord-20473a9dd9354595a0c21daec6f1d3f8
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653048B2

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