Dimethylamine → 2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-N,N-dimethyl-2-(4-(quinolin-7-yl)phenyl)acetamide

HRID 1525851

Reaktionsgleichung

Reaktionsgleichung von HRID 1525851
[CH:1]1([N:4]2[CH2:9][C:8]3([CH2:14][CH2:13][N:12]([CH:15]([C:19]4[CH:24]=[CH:23][C:22]([C:25]5[CH:34]=[C:33]6[C:28]([CH:29]=[CH:30][CH:31]=[N:32]6)=[CH:27][CH:26]=5)=[CH:21][CH:20]=4)[C:16]([OH:18])=O)[CH2:11][CH2:10]3)[O:7][CH2:6][C:5]2=[O:35])[CH2:3][CH2:2]1.[CH:36]([N:39](C(C)C)[CH2:40]C)(C)C.[Cl-].ClC1N(C)CC[N+]=1C.CNC>CN(C)C=O.C1COCC1>[CH:1]1([N:4]2[CH2:9][C:8]3([CH2:10][CH2:11][N:12]([CH:15]([C:19]4[CH:24]=[CH:23][C:22]([C:25]5[CH:34]=[C:33]6[C:28]([CH:29]=[CH:30][CH:31]=[N:32]6)=[CH:27][CH:26]=5)=[CH:21][CH:20]=4)[C:16]([N:39]([CH3:40])[CH3:36])=[O:18])[CH2:13][CH2:14]3)[O:7][CH2:6][C:5]2=[O:35])[CH2:2][CH2:3]1

Komponenten

7

Edukt 4

HCID 674Dimethylamine2×HCID 81531DiisopropylethylamineHCID 101763062-Chloro-1,3-dimethylimidazolinium chloride2×HCID 712708152-(4-Cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(4-(quinolin-7-yl)phenyl)acetic acid

Produkt 1

HCID 712711652-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-N,N-dimethyl-2-(4-(quinolin-7-yl)phenyl)acetamideAusbeute 26 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of 2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(4-(quinolin-7-yl)phenyl)acetic acid (0.191 mmol) in N,N-dimethylformamide (1 mL) was treated with diisopropylethylamine (0.573 mmol) and 2-chloro-1,3-dimethyl-4,5-dihydro-1H-imidazol-3-ium chloride (25% in dichloromethane, 0.108 mL) at room temperature. The reaction was stirred for 10 min at which point dimethylamine (2M in THF, 0.286 mmol) was added in one portion. The reaction was allowed to stir overnight, at which point additional dimethylamine (50 μL of a 2M solution in THF) and 2-chloro-1,3-dimethyl-4,5-dihydro-1H-imidazol-3-ium chloride (25% in dichloromethane, 0.030 mL) was added. The reaction mixture was stirred for an additional 30 minutes and then concentrated in vacuo. The crude material was purified by reverse phase HPLC (5-35% acetonitrile with 0.1% TFA/water with 0.1% TFA). The product fractions were combined, the pH was adjusted to ˜10 with 30% w/v ammonium hydroxide solution, and the mixture was extracted with dichloromethane three times. The combined organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford the title compound as a white solid (26%). MS(ES)+ m/e 499.4 [M+H]+.

Aufarbeitung

  1. additionwas added in one portion
  2. additionwas added
  3. concentrationconcentrated in vacuo
  4. customThe crude material was purified by reverse phase HPLC (5-35% acetonitrile with 0.1% TFA/water with 0.1% TFA)
  5. extractionthe mixture was extracted with dichloromethane three times
  6. dry with materialThe combined organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-280ef0f224db4f6c995132ddfa9c7912
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09084794B2

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