Carbonic acid, rubidium salt (1:2) → 3-methoxy-2,2-dimethylpropionic acid 5-[(R)-[3-(2-acetoxyethoxy)-2-fluoro-5-methoxyphenyl]-(4-{amino[2-methylallyloxycarbonylimino]methyl}phenylamino)methyl]-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl ester

HRID 2089693

Reaktionsgleichung

Reaktionsgleichung von HRID 2089693
[NH2:1][C:2](=[N:39][C:40]([O:42][CH2:43][C:44]([CH3:46])=[CH2:45])=[O:41])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C@@H: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[CH2:48][O:49][C:50](=[O:57])[C:51]([CH3:56])([CH3:55])[CH2:52][O:53][CH3:54].C(=O)([O-])[O-].[Rb+].[Rb+].CN(C)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]([C@@H:10]([NH:9][C:6]2[CH:5]=[CH:4][C:3]([C:2]([NH2:1])=[N:39][C:40]([O:42][CH2:43][C:44]([CH3:46])=[CH2:45])=[O:41])=[CH:8][CH:7]=2)[C:27]2[N:31]=[C:30]([O:32][CH2:48][O:49][C:50](=[O:57])[C:51]([CH3:56])([CH3:55])[CH2:52][O:53][CH3:54])[N:29]([C:33]3[N:38]=[CH:37][CH:36]=[CH:35][N:34]=3)[N:28]=2)[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=1)(=[O:20])[CH3:19]

Komponenten

7

Edukt 4

HCID 11431Carbonic acid, rubidium salt (1:2)HCID 31374DimethylacetamideHCID 144596933-Methoxy-2,2-dimethylpropionic acid chloromethyl esterHCID 136334037Acetic acid 2-{3-[(R)-{4-[amino(2-methylallyloxycarbonylimino)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 674711843-methoxy-2,2-dimethylpropionic acid 5-[(R)-[3-(2-acetoxyethoxy)-2-fluoro-5-methoxyphenyl]-(4-{amino[2-methylallyloxycarbonylimino]methyl}phenylamino)methyl]-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl esterAusbeute 45,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

Under nitrogen atmosphere, a mixture of acetic acid 2-{3-[(R)-{4-[amino(2-methylallyloxycarbonylimino)methyl]phenylamino}-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]-2-fluoro-5-methoxyphenoxyl}ethyl ester (1.0 g, 1.57 mmol), 3-methoxy-2,2-dimethylpropionic acid chloromethyl ester (598 mg, 3.31 mmol), rubidium carbonate (255 mg, 1.10 mmol), and N,N-dimethylacetamide (20 mL) was stirred at 85° C. for 75 minutes. After cooling to room temperature, ethyl acetate (100 mL) and water (100 mL) were added to the reaction mixture. The organic layer was collected, sequentially washed with water (100 mL) and saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The desiccant was filtered off, and the filtrate obtained was concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate) to obtain the captioned compound (560 mg) as a solid.

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. customThe organic layer was collected
  3. washsequentially washed with water (100 mL) and saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationThe desiccant was filtered off
  6. customthe filtrate obtained
  7. concentrationwas concentrated under reduced pressure
  8. customThe residue obtained
  9. customwas purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-58d7605c9e0d4d59b0f924e48505feb9
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08436009B2

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