醋酸 → (5-Chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-pyridin-3-ylamino)-acetic Acid Ethyl Ester

HRID 11720

反应方程式

HRID 11720 反应方程式
[NH2:1][C:2]1[C:3]([O:9][CH2:10][C:11]([N:13]2[CH2:18][C@H:17]([CH3:19])[N:16]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[CH2:15][C@H:14]2[CH3:28])=[O:12])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[C:29]([O:33][CH2:34][CH3:35])(=[O:32])[CH:30]=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([BH3-])#N.[Na+]>ClCCCl.O>[CH2:34]([O:33][C:29](=[O:32])[CH2:30][NH:1][C:2]1[C:3]([O:9][CH2:10][C:11]([N:13]2[CH2:18][C@H:17]([CH3:19])[N:16]([CH2:20][C:21]3[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=3)[CH2:15][C@H:14]2[CH3:28])=[O:12])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1)[CH3:35]

参与物

8

反应物 5

HCID 176醋酸2 次HCID 70211乙醛酸乙酯2 次HCID 5003444氰基硼氢化钠HCID 5049666三乙酰氧基硼氢化钠HCID 696555902-(3-Amino-5-chloro-pyridin-2-yloxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone

产物 1

HCID 69655410(5-Chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-pyridin-3-ylamino)-acetic Acid Ethyl Ester收率 66.3%

试剂、催化剂与溶剂 2

HCID 111,2-二氯乙烷溶剂HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂

实验过程

To a solution of 2-(3-amino-5-chloro-pyridin-2-yloxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.105 g, 0.26 mmol) in 1,2-dichloroethane (2 mL) was added ethyl glyoxylate (0.050 mL, ˜0.5 mmol, 50% solution in toluene), acetic acid (0.016 mL, 0.28 mmol) and sodium triacetoxyborohydride (0.085 g, 0.40 mmol). The reaction was stirred at ambient temperature for 18 hours. Additional ethyl glyoxylate (0.050 mL, ˜0.5 mmol, 50% solution in toluene) and acetic acid (0.016 mL, 0.28 mmol) were added and the reaction was warmed to reflux for 3 hours. The reaction was then cooled to ambient temperature, sodium cyanoborohydride (˜0.030 g, 0.48 mmol) was added and the reaction was stirred at ambient temperature for 18 hours. The reaction was diluted with water and extracted with methylene chloride. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. Flash chromatography on silica gel provided the title compound (0.085 g).

后处理

  1. temperaturethe reaction was warmed
  2. temperatureto reflux for 3 hours
  3. temperatureThe reaction was then cooled to ambient temperature
  4. stirringthe reaction was stirred at ambient temperature for 18 hours
  5. extractionextracted with methylene chloride
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

来源与证据

ORD记录
ord-f0f58e90bcac4453b21715f59bac8cc4
来源数据集
uspto-grants-2006_08
专利号
US07098212B2

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