5-Ethyl-1,2-oxazol-3-amine → N-(5-ethyl-1,2-oxazol-3-yl)-1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide

HRID 1748346Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1748346
[O:1]=[C:2]1[C:8]2=[CH:9][C:10]3[CH:11]=[CH:12][C:13]([C:16]([OH:18])=O)=[CH:14][C:15]=3[N:7]2[CH2:6][CH2:5][CH2:4][NH:3]1.CN(C([O:26][N:27]1N=N[C:29]2[CH:30]=[CH:31][CH:32]=[N:33][C:28]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N=P1N(C)CCCN1C)(C)(C)C.C(C1ON=C(N)C=1)C>C1COCC1.CN(C=O)C>[CH2:31]([C:30]1[O:26][N:27]=[C:28]([NH:33][C:16]([C:13]2[CH:12]=[CH:11][C:10]3[CH:9]=[C:8]4[C:2](=[O:1])[NH:3][CH2:4][CH2:5][CH2:6][N:7]4[C:15]=3[CH:14]=2)=[O:18])[CH:29]=1)[CH3:32]

Komponenten

7

Edukt 4

HCID 50943815-Ethyl-1,2-oxazol-3-amineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672357061-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxylic acid2×HCID 178480484HCID 178480484, Verbindung

Produkt 1

HCID 68323382N-(5-ethyl-1,2-oxazol-3-yl)-1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamideAusbeute 5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxylic acid (Intermediate J, 75 mg, 0.31 mmol) in THF (2 mL) and DMF (0.5 mL) is added HATU (128 mg, 0.34 mmol). The mixture is stirred at room temperature for 1 h, after which polystyrene bound 2-tert-butylimino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (419 mg, 0.92 mmol) is added. The mixture is stirred at room temperature for 10 min and 5-ethyl-3-aminoisoxazole (103 mg, 0.92 mmol) is added. The reaction is stirred at 60° C. for 16 h and is then cooled to room temperature. The mixture is filtered, washing with methanol and the filtrate is concentrated under reduced pressure. The residue is purified via preparative HPLC using a gradient elution from 10-90% acetonitrile/water with 0.1% TFA to obtain the title compound (5 mg, 5%). LCMS: 339.20 (M+H+). (System V1)

Aufarbeitung

  1. additionis added
  2. stirringThe mixture is stirred at room temperature for 10 min
  3. stirringThe reaction is stirred at 60° C. for 16 h
  4. temperatureis then cooled to room temperature
  5. filtrationThe mixture is filtered
  6. washwashing with methanol
  7. concentrationthe filtrate is concentrated under reduced pressure
  8. customThe residue is purified via preparative HPLC
  9. washa gradient elution from 10-90% acetonitrile/water with 0.1% TFA

Quellen und Nachweise

ORD-Eintrag
ord-e26dde735a28448a805e7175d4243b87
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09150577B2

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