Acetic Acid → HCID 178433951, compound

HRID 1407817Notes

Reaction equation

HRID 1407817 reaction equation
[O:1]=[C:2]1[C:10]2([CH2:14][O:13][C:12]3[CH:15]=[C:16]4[C:20](=[CH:21][C:11]2=3)[CH2:19][CH2:18][O:17]4)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:22][C:23]1[CH:31]=[CH:30][C:26]([C:27]([NH2:29])=O)=[CH:25][CH:24]=1.CO[C:34](OC)([N:36](C)C)[CH3:35].C(O)(=O)C.O.[NH2:46]N>O1CCOCC1>[CH3:35][C:34]1[NH:29][C:27]([C:26]2[CH:30]=[CH:31][C:23]([CH2:22][N:3]3[C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[C:10]4([CH2:14][O:13][C:12]5[CH:15]=[C:16]6[C:20](=[CH:21][C:11]4=5)[CH2:19][CH2:18][O:17]6)[C:2]3=[O:1])=[CH:24][CH:25]=2)=[N:46][N:36]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 24654Hydrazine hydrate (1:1)HCID 878351,1-Dimethoxyethyl(dimethyl)amineHCID 59352778HCID 59352778, compound

Product 1

HCID 178433951HCID 178433951, compoundYield 16.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-[(2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)methyl]benzamide (0.40 g, 0.96 mmol) in 1,4-dioxane (15 mL) was added N,N-dimethylacetamide dimethyl acetal (1.42 mL, 9.71 mmol). The reaction was heated to reflux for 18 h, concentrated in vacuo. To the above residue were added acetic acid (15 mL) and hydrazine monohydrate (0.15 mL, 3.17 mmol). The reaction was stirred at 90° C. for 6 h, cooled to ambient temperature, quenched with saturated sodium bicarbonate (15 mL), and extracted with chloroform. The combined organic solution was washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography with 5% methanol in ethyl acetate, and recrystallized from dichloromethane and hexanes to afford 1′-[4-(5-methyl-4H-1,2,4-triazol-3-yl)benzyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one (0.07 g, 16%) as a colorless solid: mp 169-180° C. (hexanes); 1H NMR (300 MHz, CDCl3) δ10.72 (s, 1H), 8.01 (d, J=8.1 Hz, 2H), 7.41 (d, J=8.1 Hz, 2H), 7.15 (d, J=7.5 Hz, 2H), 7.01 (t, J=7.5 Hz, 1H), 6.79 (d, J=7.7 Hz, 1H), 6.45 (s, 1H), 6.40 (s, 1H), 5.19-4.09 (m, 4H), 4.53-4.47 (m, 2H), 2.95-2.90 (m, 2H), 2.50 (s, 3H); 13C NMR (75 MHz, CDCl3) δ178.3, 161.9, 161.4, 141.9, 136.9, 132.7, 128.8, 127.8, 126.9, 123.9, 123.6, 120.0, 119.9, 118.8, 109.4, 93.2, 80.6, 72.4, 57.8, 44.0, 28.9, 11.7; MS (ES+) m/z 450.8 (M+1).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 18 h
  3. concentrationconcentrated in vacuo
  4. temperaturecooled to ambient temperature
  5. customquenched with saturated sodium bicarbonate (15 mL)
  6. extractionextracted with chloroform
  7. washThe combined organic solution was washed with water and brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated in vacuo
  11. customThe residue was purified by column chromatography with 5% methanol in ethyl acetate
  12. customrecrystallized from dichloromethane and hexanes

Sources & evidence

ORD record
ord-38d2bc83cadf4804b1fc88761a6146c4
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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