Dimethylformamide → n-Cyclobutyl-1'-methyl-2'-oxo-1',2,2',3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indole]-4'-carboxamide

HRID 2385543Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2385543
[CH3:1][N:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([C:11](OC3C=CC=CC=3)=[O:12])[C:5]=2[C:4]2([C:31]3[C:22](=[CH:23][C:24]4[O:29][CH2:28][CH2:27][O:26][C:25]=4[CH:30]=3)[O:21][CH2:20]2)[C:3]1=[O:32].Cl.[CH:34]1([NH2:38])[CH2:37][CH2:36][CH2:35]1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH:34]1([NH:38][C:11]([C:6]2[C:5]3[C:4]4([C:31]5[C:22](=[CH:23][C:24]6[O:29][CH2:28][CH2:27][O:26][C:25]=6[CH:30]=5)[O:21][CH2:20]4)[C:3](=[O:32])[N:2]([CH3:1])[C:10]=3[CH:9]=[CH:8][CH:7]=2)=[O:12])[CH2:37][CH2:36][CH2:35]1

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 12618374Cyclobutanamine, hydrochloride (1:1)HCID 59352217Phenyl 1'-methyl-2'-oxo-1',2,2',3-tetrahydrospiro[furo[2,3-g][1,4]-benzodioxine-8,3'-indole]-4'-carboxylate

Produkt 1

HCID 59352448n-Cyclobutyl-1'-methyl-2'-oxo-1',2,2',3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indole]-4'-carboxamideAusbeute 17 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

Phenyl 1′-methyl-2′-oxo-1′,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]-benzodioxine-8,3′-indole]-4′-carboxylate (0.30 g, 0.70 mmol), cyclobutylamine hydrochloride (0.23 g, 2.1 mmol), potassium carbonate (0.39 g, 2.8 mmol) and N,N-dimethylformamide (3.0 mL) were added to a microwave reaction vessel. The reaction was heated at 110° C. for 1 h in a microwave reactor, allowed to cool to ambient temperature, poured into water (25 mL) and extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with 1 M hydrochloric acid (50 mL) and brine (50 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with a 20% to 100% gradient of ethyl acetate in hexanes followed by recrystallization from dichloromethane/diethyl ether to afford N-cyclobutyl-1′-methyl-2′-oxo-1′,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indole]-4′-carboxamide (0.045 g, 17%) as a colorless solid: mp 128-129° C. (dichloromethane/diethyl ether); 1H NMR (300 MHz, CDCl3) δ 7.41-7.33 (m, 1H), 7.26-7.21 (m, 1H), 6.97-6.93 (m, 1H), 6.51 (s, 1H), 6.20 (s, 1H), 5.46 (d, J=6.65 Hz, 1H), 4.96-4.81 (m, 2H), 4.35-4.01 (m, 5H), 3.25 (s, 3H), 2.27-2.09 (m, 2H), 1.70-1.40 (m, 4H); MS (ES+) m/z 407.0 (M+1). N,N,1′-trimethyl-2′-oxo-1,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indole]-4′-carboxamide (0.12 g, 37%) was isolated as a byproduct from the synthesis of N-cyclobutyl-1′-methyl-2′-oxo-1′,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indole]-4′-carboxamide, obtained as colorless solid: mp 218-221° C. (dichloromethane/diethyl ether); 1H NMR (300 MHz, CDCl3) 7.32 (dd, J=7.8, 7.8 Hz, 1H), 6.91-6.84 (m, 2H), 6.44 (s, 1H), 6.22 (s, 1H), 5.05 (d, J=8.8 Hz, 1H), 4.79 (d, J=8.8 Hz, 1H), 4.20-4.04 (m, 4H), 3.28 (s, 3H), 2.79 (s, 3H), 2.19 (s, 3H); MS (ES+) m/z 381.0 (M+1).

Aufarbeitung

  1. temperatureto cool to ambient temperature
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washThe combined organic extracts were washed with 1 M hydrochloric acid (50 mL) and brine (50 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography
  8. washeluted with a 20% to 100% gradient of ethyl acetate in hexanes
  9. customfollowed by recrystallization from dichloromethane/diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-8847b8427a04478d87c47a8724ee5be8
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08263606B2

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