Dimethylformamide → 3-methoxy-2,2-dimethylpropionic acid 5-[[3-(2-acetoxyethoxy)-2-fluoro-5-methoxyphenyl]-(4-{amino[benzoylimino]methyl}phenylamino)methyl]-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl ester

HRID 2089637

反応式

HRID 2089637 の反応式
[NH2:1][C:2](=[N:39][C:40](=[O:47])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH: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[CH2:49][O:50][C:51](=[O:58])[C:52]([CH3:57])([CH3:56])[CH2:53][O:54][CH3:55].C(=O)([O-])O.[K+].CN(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]([CH:10]([NH:9][C:6]2[CH:5]=[CH:4][C:3]([C:2]([NH2:1])=[N:39][C:40](=[O:47])[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[CH:8][CH:7]=2)[C:27]2[N:31]=[C:30]([O:32][CH2:49][O:50][C:51](=[O:58])[C:52]([CH3:57])([CH3:56])[CH2:53][O:54][CH3:55])[N:29]([C:33]3[N:34]=[CH:35][CH:36]=[CH:37][N:38]=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 6228DimethylformamideHCID 516893Potassium BicarbonateHCID 144596933-Methoxy-2,2-dimethylpropionic acid chloromethyl esterHCID 136334025Acetic acid 2-{3-[(4-{amino[benzoylimino]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 674705203-methoxy-2,2-dimethylpropionic acid 5-[[3-(2-acetoxyethoxy)-2-fluoro-5-methoxyphenyl]-(4-{amino[benzoylimino]methyl}phenylamino)methyl]-2-pyrimidin-2-yl-2H-[1,2,4]triazol-3-yloxymethyl ester収率 34.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
55 °C

実験手順

Under nitrogen atmosphere, a mixture of acetic acid 2-{3-[(4-{amino[benzoylimino]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 (441 mg), 3-methoxy-2,2-dimethylpropionic acid chloromethyl ester (Example 4a, 373 mg), potassium hydrogen carbonate (241 mg), and DMF (20 mL) was stirred at 55° C. for 15 hours. The resulting mixture was poured into ethyl acetate (200 mL) and water (50 mL). After shaking the resulting mixture, the organic layer was collected, sequentially washed twice with water (50 mL) and with saturated aqueous sodium chloride solution (50 mL), and dried over anhydrous magnesium sulfate. The resulting mixture was filtered, and the filtrate obtained was concentrated under reduced pressure. The residue obtained was purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate) to obtain the captioned compound (184 mg).

後処理

  1. stirringAfter shaking the resulting mixture
  2. customthe organic layer was collected
  3. washsequentially washed twice with water (50 mL) and with saturated aqueous sodium chloride solution (50 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationThe resulting mixture was filtered
  6. customthe filtrate obtained
  7. concentrationwas concentrated under reduced pressure
  8. customThe residue obtained
  9. customwas purified by NAM silica gel column chromatography (mixed solvent of methanol-ethyl acetate)

出典と根拠

ORDレコード
ord-d830da76c9c849bdbf03dfbea23a9e7b
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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