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

反応式

HRID 2089693 の反応式
[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]

参加物

7

反応物 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

生成物 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 ester収率 45.8%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
85 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-58d7605c9e0d4d59b0f924e48505feb9
出典データセット
uspto-grants-2013_05
特許番号
US08436009B2

関連ノート

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