Hydrochloric Acid → HCID 58486241, compound

HRID 1410334Notes

Reaction equation

HRID 1410334 reaction equation
[NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=O)[C:2]1=[O:3].[H-].[Na+].Br[CH2:15][CH2:16][O:17][CH3:18].O.NN.Cl>CN(C=O)C.CS(C)=O>[CH3:18][O:17][CH2:16][CH2:15][N:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:4][C:2]1=[O:3]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7054IsatinHCID 24654Hydrazine hydrate (1:1)HCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl ether

Product 1

HCID 58486241HCID 58486241, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of isatin (2.94 g, 20 mmol) in DMF (40 mL) at 0° C. was added 60% NaH (1.00 g, 25 mmol) portionwise. After addition, the resulting mixture was stirred for 15 min at 0° C., then 1-bromo-2-methoxyethane (2.35 mL, 25 mmol) was added dropwise over 2 min. The resulting mixture was stirred for 10 min at 0° C., then 0/N at rt, then cooled to 0° C., and quenched with saturated NH4Cl, ice, and H2O. The product was extracted with EtOAc (150 mL×2) and dried (Na2SO4). Removal of solvents gave a dark orange red liquid which was redissolved in DMSO (10 mL). Hydrazine hydrate (2 mL) was added dropwise over 7 min. After addition, the reaction mixture was stirred for 5 min at rt, then 2 h at 140° C. (oil temp.) before cooling to rt. Ice/H2O (20 mL) was added, followed by 6 M HCl (7 mL, 42 mmol), and the resulting mixture was stirred for 30 min at rt. Additional ice/H2O (40 mL) was added, and the mixture was extracted with EtOAc (50 mL×3). Purification by flash chromatography (gradient: 0 to 40% EtOAc in hexane) afforded the title compound (orange liquid, 2.32 g, 61% over 2 steps). 1H NMR (400 MHz, DMSO-d6) δ 7.26-7.20 (m, 2H), 7.03 (d, J=8.0 Hz, 1H), 6.98 (t, J=7.4 Hz, 1H), 3.82 (t, J=5.6 Hz, 2H), 3.55 (s, 2H), 3.52 (t, J=5.8 Hz, 2H), 3.22 (s, 3H); MS ESI 191.8 [M+H]+, calcd for [C11H13NO2+H]+ 192.1.

Workup

  1. additionAfter addition
  2. stirringThe resulting mixture was stirred for 10 min at 0° C.
  3. temperature0/N at rt, then cooled to 0° C.
  4. customquenched with saturated NH4Cl, ice, and H2O
  5. extractionThe product was extracted with EtOAc (150 mL×2)
  6. dry with materialdried (Na2SO4)
  7. customRemoval of solvents
  8. customgave a dark orange red liquid which
  9. additionAfter addition
  10. stirringthe reaction mixture was stirred for 5 min at rt
  11. temperature2 h at 140° C. (oil temp.) before cooling to rt
  12. stirringthe resulting mixture was stirred for 30 min at rt
  13. extractionthe mixture was extracted with EtOAc (50 mL×3)
  14. customPurification by flash chromatography (gradient: 0 to 40% EtOAc in hexane)

Sources & evidence

ORD record
ord-be2165f9499b4862a4864b30a42eb488
Source dataset
uspto-grants-2014_12
Patent number
US08921545B2

Reaction notes

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