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

HRID 2089697

Reaktionsgleichung

Reaktionsgleichung von HRID 2089697
[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.[CH2:47]([CH:49]([O:52][C:53](=[O:57])[O:54][CH2:55]Cl)[CH2:50][CH3:51])[CH3:48].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O.C(OCC)(=O)C>[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]([C:27]2[N:31]=[C:30]([O:32][CH2:55][O:54][C:53]([O:52][CH:49]([CH2:50][CH3:51])[CH2:47][CH3:48])=[O:57])[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:7][CH:8]=1

Komponenten

7

Edukt 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 54403423Chloromethyl pentan-3-yl carbonateHCID 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 86677416Acetic acid 2-(3-{(R)-(4-{amino[2-methylallyloxycarbonylimino]methyl}phenylamino)-[5-(1-ethylpropoxycarbonyloxymethoxy)-1-pyrimidin-2-yl-1H-[1,2,4]triazol-3-yl]methyl}-2-fluoro-5-methoxyphenoxy)ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

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 (Example 45, 300 mg), carbonic acid chloromethyl ester 1-ethylpropyl ester [CAS No. 176310-42-2] (177 mg), potassium carbonate (80 mg) and N,N-dimethylformamide (5 mL) was stirred at 85° C. for 60 minutes. After cooling the mixture to room temperature, ethyl acetate and water were added thereto. The organic layer was collected, the aqueous layer was reextracted with ethyl acetate, and all the organic layers were combined. The organic layer was sequentially washed with water and with 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-methanol) to obtain the captioned compound (130 mg) as a solid.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-2cb91cbfcfbf49ddb481e99d6d0ac438
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08436009B2

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