Dimethylformamide → N,1'-dimethyl-2'-oxo-1',2,2',3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indole]-4'-carboxamide

HRID 1407923Notes

Reaction equation

HRID 1407923 reaction equation
[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.CN.C(=O)([O-])[O-].[K+].[K+].[CH3:42][N:43](C)C=O>O>[CH3:42][NH:43][C:11]([C:6]1[C:5]2[C:4]3([C:31]4[C:22](=[CH:23][C:24]5[O:29][CH2:28][CH2:27][O:26][C:25]=5[CH:30]=4)[O:21][CH2:20]3)[C:3](=[O:32])[N:2]([CH3:1])[C:10]=2[CH:9]=[CH:8][CH:7]=1)=[O:12]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 6364545Methylamine hydrochloride2×HCID 59352217Phenyl 1'-methyl-2'-oxo-1',2,2',3-tetrahydrospiro[furo[2,3-g][1,4]-benzodioxine-8,3'-indole]-4'-carboxylate

Product 1

HCID 59352682N,1'-dimethyl-2'-oxo-1',2,2',3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indole]-4'-carboxamideYield 32%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

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), methylamine hydrochloride (0.12 g, 1.8 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 100° C. for 0.5 h in a microwave reactor. Further, methylamine hydrochloride (0.20 g, 3.0 mmol) was added and the mixture was heated at 100° C. for an additional 45 min in a microwave reactor. The mixture 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 brine (2×50 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. The product was precipitated from dichloromethane with diethyl ether and subsequently recrystallized from ethyl acetate to afford N,1′-dimethyl-2′-oxo-1′,2,2′,3-tetrahydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indole]-4′-carboxamide (0.08 g, 32%) as a colorless solid: mp 120-122° C. (ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 7.41-7.31 (m, 1H), 7.25-7.19 (m, 1H), 6.98-6.93 (m, 1H), 6.49 (s, 1H), 6.20 (s, 1H), 5.19 (d, J=3.2 Hz, 1H), 4.87 (s, 2H), 4.21-4.08 (m, 4H), 3.26 (s, 3H), 2.64 (d, J=4.9 Hz, 3H); MS (ES+) m/z 366.9 (M+1).

Workup

  1. temperaturethe mixture was heated at 100° C. for an additional 45 min in a microwave reactor
  2. temperatureto cool to ambient temperature
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. washThe combined organic extracts were washed with brine (2×50 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe product was precipitated from dichloromethane with diethyl ether
  9. customsubsequently recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-02e04664b4c44e718be93478a37413db
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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