Pyridine → 3-[[6-[(Chloroacetyl)amino]-1-oxohexyl]amino]-alpha-ethyl-2,4,6-triiodobenzenepropanoic acid

HRID 2258389

反応式

HRID 2258389 の反応式
[CH3:1][N:2]([CH:4]=[O:5])C.[C:6]([Cl:11])(=O)[C:7](Cl)=[O:8].[N:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.NC1[C:20]([I:34])=[C:21]([CH2:27][CH:28]([CH2:32][CH3:33])[C:29]([OH:31])=[O:30])[C:22]([I:26])=[CH:23][C:24]=1[I:25].[OH-].[Na+]>C(Cl)Cl.C1COCC1>[Cl:11][CH2:6][C:7]([NH:12][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][C:4]([NH:2][C:1]1[C:20]([I:34])=[C:21]([CH2:27][CH:28]([CH2:32][CH3:33])[C:29]([OH:31])=[O:30])[C:22]([I:26])=[CH:23][C:24]=1[I:25])=[O:5])=[O:8]

参加物

8

反応物 5

HCID 1049PyridineHCID 3735Iopanoic AcidHCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 65578Oxalyl chloride

生成物 1

HCID 229214013-[[6-[(Chloroacetyl)amino]-1-oxohexyl]amino]-alpha-ethyl-2,4,6-triiodobenzenepropanoic acid収率 79.3%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
40 °C

実験手順

In a solution of 43.9 g of DMF (0.6 mol) in 700 ml of CH2Cl2, kept at a temperature of 5° C. and under nitrogen atmosphere, 109.2 g of oxalyl chloride (0.86 mol) are dropwise added, obtaining a white precipitate. After 1 h, the solvent and the oxalyl chloride excess are removed under reduced pressure. The residue is suspended in 1000 ml of THF and 500 ml of MeCN and in the suspension kept at a temperature of 5° C., a solution of 130 g of 6-[(chloroacetyl)amino]hexanoic acid (prepared according to the procedure described in J. Chromatography, 1984, 292, 369-382) (0.63 mol) is dropwise added and 47.5 g of pyridine (0.6 mol) in 500 ml of THF. The reaction mixture is then heated to 40° C. for 2 h. A solution of 171.3 g of 3-amino-α-ethyl-2,4,6-triiodobenzenepropanoic acid (CAS RN 96-83-3) (0.30 mol) in 300 ml of THF is slowly added and the whole is heated for 3 h at reflux. The solution is concentrated and the residue is dissolved in 500 ml of H2O. The pH is adjusted to 8 with 620 ml of 2N NaOH (1.24 mol) and THF is evaporated under reduced pressure. The aqueous solution is extracted 3 times with 200 ml portions of CH2Cl2. The organic phases are collected and washed with 200 ml of H2O at pH 8. The aqueous phases are acidified with 200 ml of 37% HCl yielding a precipitate, which is filtered. 181 g of 3-[[6-[(chloroacetyl)amino]-1-oxohexyl]amino]-α-ethyl-2,4,6-triiodobenzenepropanoic acid (0.238 mol) are obtained.

後処理

  1. customkept at a temperature of 5° C. and under nitrogen atmosphere
  2. customobtaining a white precipitate
  3. customthe solvent and the oxalyl chloride excess are removed under reduced pressure
  4. customkept at a temperature of 5° C.
  5. customa solution of 130 g of 6-[(chloroacetyl)amino]hexanoic acid (prepared
  6. additionChromatography, 1984, 292, 369-382) (0.63 mol) is dropwise added
  7. temperaturethe whole is heated for 3 h
  8. temperatureat reflux
  9. concentrationThe solution is concentrated
  10. dissolutionthe residue is dissolved in 500 ml of H2O
  11. customis evaporated under reduced pressure
  12. extractionThe aqueous solution is extracted 3 times with 200 ml portions of CH2Cl2
  13. customThe organic phases are collected
  14. washwashed with 200 ml of H2O at pH 8
  15. filtrationis filtered

出典と根拠

ORDレコード
ord-b2165f3800e5446080e6f9b7e2dcf808
出典データセット
uspto-grants-1997_08
特許番号
US05660814

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