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

Reaction equation

HRID 2089702 reaction equation
[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

Participants

5

Reactant 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

Product 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

Conditions

Temperature
85 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-596a37aee1054ea7b96f472188a3eb5f
Source dataset
uspto-grants-2013_05
Patent number
US08436009B2

Linked notes

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