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

HRID 2089701

Reaktionsgleichung

Reaktionsgleichung von HRID 2089701
[CH3:1][C:2](=[CH2:43])[CH2:3][O:4][C:5](=[O:42])[N:6]=[C:7]([C:9]1[CH:14]=[CH:13][C:12]([NH:15][C@H:16]([C:29]2[CH:34]=[C:33]([O:35][CH3:36])[CH:32]=[C:31]([O:37][CH2:38][CH2:39][OH:40])[C:30]=2[F:41])[C:17]2[NH:21][C:20](=[O:22])[N:19]([C:23]3[N:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[N:18]=2)=[CH:11][CH:10]=1)[NH2:8].[F:44][CH2:45][C:46]([O:49][C:50](=[O:54])[O:51][CH2:52]Cl)([CH3:48])[CH3:47].C(=O)([O-])[O-].[Rb+].[Rb+]>CN(C)C(=O)C>[F:44][CH2:45][C:46]([O:49][C:50](=[O:54])[O:51][CH2:52][O:22][C:20]1[N:19]([C:23]2[N:24]=[CH:25][CH:26]=[CH:27][N:28]=2)[N:18]=[C:17]([C@H:16]([NH:15][C:12]2[CH:13]=[CH:14][C:9]([C:7]([NH2:8])=[N:6][C:5]([O:4][CH2:3][C:2]([CH3:1])=[CH2:43])=[O:42])=[CH:10][CH:11]=2)[C:29]2[CH:34]=[C:33]([O:35][CH3:36])[CH:32]=[C:31]([O:37][CH2:38][CH2:39][OH:40])[C:30]=2[F:41])[N:21]=1)([CH3:48])[CH3:47]

Komponenten

5

Edukt 3

HCID 11431Carbonic acid, rubidium salt (1:2)HCID 86677420Carbonic acid chloromethyl ester 2-fluoro-1,1-dimethylethyl esterHCID 136334036[1-amino(4-{[(R)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl](5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]amino}phenyl)methylene]carbamic acid 2-methylallyl ester

Produkt 1

HCID 86677424Carbonic acid 5-{(R)-(4-{amino[2-methylallyloxycarbonylimino]methyl}phenylamino)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl]methyl}-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl ester 2-fluoro-1,1-dimethylethyl esterAusbeute 16,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

Under nitrogen atmosphere, a mixture of [1-amino(4-{[(R)-[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl](5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]amino}phenyl)methylene]carbamic acid 2-methylallyl ester (Example 44, 474 mg), carbonic acid chloromethyl ester 2-fluoro-1,1,dimethylethyl ester (295 mg), rubidium carbonate (166 mg) and N,N-dimethylacetamide (15 mL) was stirred at 85° C. for 60 minutes. After cooling the mixture to room temperature, the reaction solution was concentrated under reduced pressure. The obtained residue was purified by reverse phase silica gel column chromatography (mixed solvent of methanol-water containing 0.1% of acetic acid), and then the obtained compound was further purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate-methanol) to obtain the captioned compound (98 mg).

Aufarbeitung

  1. temperatureAfter cooling the mixture to room temperature
  2. concentrationthe reaction solution was concentrated under reduced pressure
  3. customThe obtained residue was purified by reverse phase silica gel column chromatography (mixed solvent of methanol-water containing 0.1% of acetic acid)
  4. customthe obtained compound was further purified by silica gel column chromatography (mixed solvent of heptane-ethyl acetate-methanol)

Quellen und Nachweise

ORD-Eintrag
ord-308506742aa445d98dbbd4158746e2db
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08436009B2

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