Dimethylformamide → 3-methoxy-2,2-dimethylpropionic acid 5-[[3-(2-acetoxyethoxy)-2-fluoro-5-methoxyphenyl]-(4-{amino[benzoylimino]methyl}phenylamino)methyl]-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl ester

HRID 2089637

Reaktionsgleichung

Reaktionsgleichung von HRID 2089637
[NH2:1][C:2](=[N:39][C:40](=[O:47])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]([C:27]2[NH:31][C:30](=[O:32])[N:29]([C:33]3[N:38]=[CH:37][CH:36]=[CH:35][N:34]=3)[N:28]=2)[C:11]2[C:12]([F:26])=[C:13]([CH:21]=[C:22]([O:24][CH3:25])[CH:23]=2)[O:14][CH2:15][CH2:16][O:17][C:18](=[O:20])[CH3:19])=[CH:5][CH:4]=1.Cl[CH2:49][O:50][C:51](=[O:58])[C:52]([CH3:57])([CH3:56])[CH2:53][O:54][CH3:55].C(=O)([O-])O.[K+].CN(C=O)C>O.C(OCC)(=O)C>[C:18]([O:17][CH2:16][CH2:15][O:14][C:13]1[C:12]([F:26])=[C:11]([CH:10]([NH:9][C:6]2[CH:5]=[CH:4][C:3]([C:2]([NH2:1])=[N:39][C:40](=[O:47])[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[CH:8][CH:7]=2)[C:27]2[N:31]=[C:30]([O:32][CH2:49][O:50][C:51](=[O:58])[C:52]([CH3:57])([CH3:56])[CH2:53][O:54][CH3:55])[N:29]([C:33]3[N:34]=[CH:35][CH:36]=[CH:37][N:38]=3)[N:28]=2)[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=1)(=[O:20])[CH3:19]

Komponenten

7

Edukt 4

HCID 6228DimethylformamideHCID 516893Potassium BicarbonateHCID 144596933-Methoxy-2,2-dimethylpropionic acid chloromethyl esterHCID 136334025Acetic acid 2-{3-[(4-{amino[benzoylimino]methyl}phenylamino)-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]-2-fluoro-5-methoxyphenoxy)ethyl ester

Produkt 1

HCID 674705203-methoxy-2,2-dimethylpropionic acid 5-[[3-(2-acetoxyethoxy)-2-fluoro-5-methoxyphenyl]-(4-{amino[benzoylimino]methyl}phenylamino)methyl]-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl esterAusbeute 34,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
55 °C

Versuchsvorschrift

Under nitrogen atmosphere, a mixture of acetic acid 2-{3-[(4-{amino[benzoylimino]methyl}phenylamino)-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]-2-fluoro-5-methoxyphenoxy)ethyl ester (441 mg), 3-methoxy-2,2-dimethylpropionic acid chloromethyl ester (Example 4a, 373 mg), potassium hydrogen carbonate (241 mg), and DMF (20 mL) was stirred at 55° C. for 15 hours. The resulting mixture was poured into ethyl acetate (200 mL) and water (50 mL). After shaking the resulting mixture, the organic layer was collected, sequentially washed twice with water (50 mL) and with saturated aqueous sodium chloride solution (50 mL), and dried over anhydrous magnesium sulfate. The resulting mixture was filtered, and the filtrate obtained was concentrated under reduced pressure. The residue obtained was purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate) to obtain the captioned compound (184 mg).

Aufarbeitung

  1. stirringAfter shaking the resulting mixture
  2. customthe organic layer was collected
  3. washsequentially washed twice with water (50 mL) and with saturated aqueous sodium chloride solution (50 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationThe resulting mixture was filtered
  6. customthe filtrate obtained
  7. concentrationwas concentrated under reduced pressure
  8. customThe residue obtained
  9. customwas purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-d830da76c9c849bdbf03dfbea23a9e7b
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08436009B2

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