Dichloromethane → {(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-[(1S)-1-methylpropyl]-2,5-dioxo-1-piperazinyl}(2,6-dimethyl-3-pyridinyl)acetic acid hydrochloride

HRID 220071Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 220071
[CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[C@H:10]1[NH:15][C:14](=[O:16])[C@@H:13]([C@@H:17]([CH3:20])[CH2:18][CH3:19])[N:12]([CH:21]([C:32]2[C:33]([CH3:39])=[N:34][C:35]([CH3:38])=[CH:36][CH:37]=2)[C:22](NC2C=CC=CC=2O)=[O:23])[C:11]1=[O:40].C(N1C=CN=C1)(N1C=CN=C1)=[O:42].[Cl:53]CCl>>[ClH:53].[CH2:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:1][CH:2]1[C@H:10]1[NH:15][C:14](=[O:16])[C@@H:13]([C@@H:17]([CH3:20])[CH2:18][CH3:19])[N:12]([CH:21]([C:32]2[C:33]([CH3:39])=[N:34][C:35]([CH3:38])=[CH:36][CH:37]=2)[C:22]([OH:42])=[O:23])[C:11]1=[O:40]

Komponenten

4

Edukt 3

HCID 6344DichloromethaneHCID 682631,1'-CarbonyldiimidazoleHCID 569495922-{(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-[(1S)-1-methylpropyl]-2,5-dioxo-1-piperazinyl}-2-(2,6-dimethyl-3-pyridinyl)-N-(2-hydroxyphenyl)acetamide2×

Produkt 1

HCID 56949593{(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-[(1S)-1-methylpropyl]-2,5-dioxo-1-piperazinyl}(2,6-dimethyl-3-pyridinyl)acetic acid hydrochlorideAusbeute 56 %

Versuchsvorschrift

2-{(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-[(1S)-1-methylpropyl]-2,5-dioxo-1-piperazinyl}-2-(2,6-dimethyl-3-pyridinyl)-N-(2-hydroxyphenyl)acetamide (24.25 g, 45 mmol) (intermediate 2) and 1,1′-carbonyldiimidazole (11.7 g, 72 mmol) were dissolved in dry dichloromethane (200 ml) and left to stand under nitrogen for 20 hours. The solvent was removed in vacuo and the residue was dissolved in acetone (200 ml) and 2N hydrochloric acid (20 ml). After stirring for 20 hours the solvent was removed in vacuo and the residue was dissolved in methanol (50 ml). The solution was applied to an aminopropyl cartridge (2×70 g) and eluted with methanol (250 ml) and then 10% acetic acid in methanol (250 ml). The required fractions were combined and evaporated in vacuo. The residue was treated with 2N hydrochloric acid and the resulting solution evaporated in vacuo to give the title compound {(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-[(1S)-1-methylpropyl]-2,5-dioxo-1-piperazinyl}(2,6-dimethyl-3-pyridinyl)acetic acid hydrochloride as a tan solid (12.21 g, 56%).

Aufarbeitung

  1. waitleft
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in acetone (200 ml)
  4. customwas removed in vacuo
  5. dissolutionthe residue was dissolved in methanol (50 ml)
  6. washeluted with methanol (250 ml)
  7. customevaporated in vacuo
  8. additionThe residue was treated with 2N hydrochloric acid
  9. customthe resulting solution evaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-8a2e2f0873da448493bd1eca96e66aa1
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08202864B2

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