Carbonic acid, rubidium salt (1:2) → Acetic acid 2-(3-{(R)-(4-{amino[2-methylallyloxycarbonylimino]methyl}phenylamino)-[5-(2-fluoro-1,1-dimethylethoxycarbonyloxymethoxy)-1-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yl]methyl}-2-fluoro-5-methoxyphenoxy)ethyl ester

HRID 2089702

Reaktionsgleichung

Reaktionsgleichung von HRID 2089702
[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.[F:47][CH2:48][C:49]([O:52][C:53](=O)[O:54]CCl)(C)C.[C:58](=O)([O-])[O-].[Rb+].[Rb+].CN(C)[C:66](=[O:68])[CH3:67]>>[NH2:1][C:2](=[N:39][C:40]([O:42][CH2:43][C:44]([CH3:46])=[CH2:45])=[O:41])[C:3]1[CH:4]=[CH:5][C:6]([NH:9][C@@H:10]([CH:27]2[N:31]=[C:30]([O:32][C:66]([O:68][C:53]([O:52][CH2:49][CH2:48][F:47])=[O:54])([CH3:58])[CH3:67])[N:29]([C:33]3[N:38]=[CH:37][CH:36]=[CH:35][N:34]=3)[NH: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:7][CH:8]=1

Komponenten

5

Edukt 4

HCID 11431Carbonic acid, rubidium salt (1:2)HCID 31374DimethylacetamideHCID 86677420Carbonic acid chloromethyl ester 2-fluoro-1,1-dimethylethyl 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 86677421Acetic acid 2-(3-{(R)-(4-{amino[2-methylallyloxycarbonylimino]methyl}phenylamino)-[5-(2-fluoro-1,1-dimethylethoxycarbonyloxymethoxy)-1-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yl]methyl}-2-fluoro-5-methoxyphenoxy)ethyl ester

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-methoxyphenoxy}ethyl ester (Example 45, 508 mg), carbonic acid chloromethyl ester 2-fluoro-1,1,dimethylethyl ester (Example 56a, 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 (104 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-596a37aee1054ea7b96f472188a3eb5f
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08436009B2

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