Acetic Acid → HCID 178481357, compound

HRID 1965803Notes

Reaction equation

HRID 1965803 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[C:7]1([C:27]3[C:18](=[CH:19][C:20]4[O:25][CH2:24][CH2:23][O:22][C:21]=4[CH:26]=3)[O:17][CH2:16]1)[C:8](=[O:15])[N:9]2[CH3:14])=O.[OH2:28].[NH2:29][NH2:30].[C:31](O)(=O)C>>[OH:28][C:31]1[NH:30][N:29]=[C:3]([C:5]2[CH:13]=[CH:12][CH:11]=[C:10]3[C:6]=2[C:7]2([C:27]4[C:18](=[CH:19][C:20]5[O:25][CH2:24][CH2:23][O:22][C:21]=5[CH:26]=4)[O:17][CH2:16]2)[C:8](=[O:15])[N:9]3[CH3:14])[CH:2]=1

Participants

4

Reactant 3

HCID 176Acetic AcidHCID 24654Hydrazine hydrate (1:1)HCID 86642199HCID 86642199, compound

Product 1

HCID 178481357HCID 178481357, compoundYield 14%

Procedure

To a suspension of 4′-(bromoacetyl)-1′-methyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.23 g, 0.53 mmol) in glacial acetic acid (5 mL) was added dropwise hydrazine hydrate (0.03 mL, 0.59 mmol) and the reaction mixture was heated at reflux for 16 h, allowed to cool to ambient temperature and was concentrated in vacuo. The crude product was triturated in dichloromethane (10 mL) and the resultant solid was recrystallized from dichloromethane/diethyl ether. Following a second recrystallization from methanol, 4′-(5-hydroxy-1H-pyrazol-3-yl)-1′-methyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.029 g, 14%) was obtained as a colorless solid: mp>250° C. (methanol); 1H NMR (300 MHz, DMSO-d6) δ11.77 (br s, 1H), 9.51 (br s, 1H), 7.49-7.39 (m, 1H), 7.22-7.09 (m, 2H), 6.41 (s, 1H), 6.15 (s, 1H), 4.76-4.42 (m, 3H), 4.25-4.02 (m, 4H), 3.19 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 177.1, 155.0, 144.7, 144.0, 137.2, 129.1, 126.5, 123.1, 121.8, 110.6, 108.8, 98.7, 90.6, 76.2, 64.2, 63.6, 57.7, 26.5; MS (ES+) m/z 391.8 (M+1).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 16 h
  3. concentrationwas concentrated in vacuo
  4. customThe crude product was triturated in dichloromethane (10 mL)
  5. customthe resultant solid was recrystallized from dichloromethane/diethyl ether
  6. customa second recrystallization from methanol

Sources & evidence

ORD record
ord-ed24667999e546e58017a1dc60962351
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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