Dichloromethane → (S)-2-(9-neopentyl-8-oxo-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)ethyl acetate

HRID 1985471Notes

Reaction equation

HRID 1985471 reaction equation
O[CH2:2][C:3]1[C:11]([CH2:12][C@H:13]2[CH2:17][CH2:16][O:15][C:14]2=[O:18])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[N:6][NH:7]2.S(Cl)(Cl)=O.[C:23](=[O:26])([O-])[O-].[K+].[K+].[CH2:29]([NH2:34])[C:30]([CH3:33])([CH3:32])[CH3:31].Cl[CH2:36]Cl>>[C:14]([O:15][CH2:16][CH2:17][C@H:13]1[C:23](=[O:26])[N:34]([CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:2][C:3]2[C:4]3[CH:5]=[N:6][NH:7][C:8]=3[CH:9]=[CH:10][C:11]=2[CH2:12]1)(=[O:18])[CH3:36]

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 79882NeopentylamineHCID 59731937(S)-3-((4-(hydroxymethyl)-1H-indazol-5-yl)methyl)-dihydrofuran-2(3H)-one

Product 1

HCID 59731999(S)-2-(9-neopentyl-8-oxo-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)ethyl acetateYield 19%

Procedure

(S)-3-((4-(hydroxymethyl)-1H-indazol-5-yl)methyl)-dihydrofuran-2(3H)-one (70 mg, 0.28 mmol), was dissolved in dichloromethane (1.5 mL). Thionyl chloride (500 μL) was added to the mixture. Reaction stirred at room temperature for 45 minutes. Mixture was concentrated. Residue was treated with dichloromethane and re-concentrated. Residue was dissolved in acetonitrile (3 mL). Potassium carbonate (150 mg, 1.1 mmol) was added to the mixture followed by neopentylamine (100 μL, 0.85 mmol). Mixture was heated at reflux for 45 minutes. Mixture was cooled to room temperature and filtered. Filtrate was concentrated in vacuo. Residue was dissolved in toluene (5 mL). Acetic acid (200 μL) was added to the mixture. Reaction was heated at reflux for 5.5 hours. Mixture was concentrated in vacuo. Preparatory HPLC purification gave the title compound as yellow solid in 19% yield. MS m/e (M−H)−=356.

Workup

  1. customReaction
  2. concentrationMixture was concentrated
  3. additionResidue was treated with dichloromethane
  4. concentrationre-concentrated
  5. dissolutionResidue was dissolved in acetonitrile (3 mL)
  6. temperatureMixture was heated
  7. temperatureat reflux for 45 minutes
  8. temperatureMixture was cooled to room temperature
  9. filtrationfiltered
  10. concentrationFiltrate was concentrated in vacuo
  11. dissolutionResidue was dissolved in toluene (5 mL)
  12. additionAcetic acid (200 μL) was added to the mixture
  13. customReaction
  14. temperaturewas heated
  15. temperatureat reflux for 5.5 hours
  16. concentrationMixture was concentrated in vacuo
  17. customPreparatory HPLC purification

Sources & evidence

ORD record
ord-c717a26510614229b368155927e720fc
Source dataset
uspto-grants-2009_06
Patent number
US07544680B2

Reaction notes

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