Water → [(4-dipropylamino-butyl)-(4-[[(1H-imidazol-2-ylmethyl)-(1-methyl-1H-imidazol-2-ylmethyl)-amino]-methyl]-benzyl)-amino]-acetic acid-2-morpholin-4-yl-ethyl ester

HRID 2080856ノート

反応式

HRID 2080856 の反応式
[CH2:1]([N:4]([CH2:36][CH2:37][CH3:38])[CH2:5][CH2:6][CH2:7][CH2:8][N:9]([CH2:32][C:33]([OH:35])=[O:34])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][N:18]([CH2:26][C:27]2[NH:28][CH:29]=[CH:30][N:31]=2)[CH2:19][C:20]2[N:21]([CH3:25])[CH:22]=[CH:23][N:24]=2)=[CH:13][CH:12]=1)[CH2:2][CH3:3].C(Cl)(Cl)Cl.[OH2:43]>>[N:4]1([CH2:36][CH2:37][O:34][C:33](=[O:35])[CH2:32][N:9]([CH2:8][CH2:7][CH2:6][CH2:5][N:4]([CH2:1][CH2:2][CH3:3])[CH2:36][CH2:37][CH3:38])[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][N:18]([CH2:26][C:27]3[NH:28][CH:29]=[CH:30][N:31]=3)[CH2:19][C:20]3[N:21]([CH3:25])[CH:22]=[CH:23][N:24]=3)=[CH:13][CH:12]=2)[CH2:5][CH2:6][O:43][CH2:2][CH2:1]1

参加物

4

反応物 3

HCID 962WaterHCID 6212ChloroformHCID 11540944[(4-dipropylamino-butyl)-(4-[[(1H-imidazol-2-ylmethyl)-(1-methyl-1H-imidazol-2-ylmethyl)-amino]-methyl]-benzyl)-amino]-acetic acid

生成物 1

HCID 11549112[(4-dipropylamino-butyl)-(4-[[(1H-imidazol-2-ylmethyl)-(1-methyl-1H-imidazol-2-ylmethyl)-amino]-methyl]-benzyl)-amino]-acetic acid-2-morpholin-4-yl-ethyl ester

実験手順

The compound (185.8 mg) obtained in Example 65-1 was dissolved in a small amount of water. The solution was added with chloroform and a 1 mol/l sodium hydroxide aqueous solution, and the organic layer and an oily substance were collected, followed by drying with anhydrous magnesium sulfate. After filtration, the solvent was distilled off. An anhydrous DMF solution (2 ml) containing the resultant sodium salt (143.6 mg) and N-(2-hydroxyethyl)morpholine (38 mg) was added with HOBt (37 mg) and WSCI hydrochloride (63 mg) and the whole was stirred overnight. After the solvent was distilled off, the resultant was dissolved in chloroform and washed with a saturated aqueous sodium hydrogen carbonate solution. The aqueous layer was extracted with chloroform and dried with anhydrous magnesium sulfate. The reaction mixture obtained by distillating the solvent off was purified through silica gel column chromatography (chloroform). The resultant was dissolved in dioxane and a salt was allowed to precipitate with a 4 mol/l hydrogen chloride/dioxane solution. After the solvent was distilled off, the solid substance was pulverized and dried under reduced pressure, thereby obtaining a hydrochloride (143,4 mg) of the subject compound as a white solid.

後処理

  1. customa 1 mol/l sodium hydroxide aqueous solution, and the organic layer and an oily substance were collected
  2. dry with materialby drying with anhydrous magnesium sulfate
  3. filtrationAfter filtration
  4. distillationthe solvent was distilled off
  5. additionAn anhydrous DMF solution (2 ml) containing the resultant sodium salt (143.6 mg) and N-(2-hydroxyethyl)morpholine (38 mg)
  6. additionwas added with HOBt (37 mg) and WSCI hydrochloride (63 mg)
  7. distillationAfter the solvent was distilled off
  8. dissolutionthe resultant was dissolved in chloroform
  9. washwashed with a saturated aqueous sodium hydrogen carbonate solution
  10. extractionThe aqueous layer was extracted with chloroform
  11. dry with materialdried with anhydrous magnesium sulfate
  12. customThe reaction mixture obtained
  13. customoff was purified through silica gel column chromatography (chloroform)
  14. dissolutionThe resultant was dissolved in dioxane
  15. customto precipitate with a 4 mol/l hydrogen chloride/dioxane solution
  16. distillationAfter the solvent was distilled off
  17. customdried under reduced pressure

出典と根拠

ORDレコード
ord-bef32d01ec484b12bc6f76a599878990
出典データセット
uspto-grants-2011_04
特許番号
US07932281B2

反応ノート

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