Hydrazine hydrate (1:1) → 1-(6-Amino-5-methoxy-2,3-dihydro-1H-indol-1-yl)-2-(dimethylamino)ethan-1-one

HRID 1014247

Reaction equation

HRID 1014247 reaction equation
[CH3:1][N:2]([CH3:20])[CH2:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:18][CH3:19])=[C:12]([N+:15]([O-])=O)[CH:13]=2)[CH2:8][CH2:7]1)=[O:5].O.NN>CO.[Fe](Cl)(Cl)Cl>[CH3:20][N:2]([CH2:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:18][CH3:19])=[C:12]([NH2:15])[CH:13]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:1]

Participants

5

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 594418292-(Dimethylamino)-1-(5-methoxy-6-nitroindolin-1-yl)ethanone

Product 1

HCID 534147641-(6-Amino-5-methoxy-2,3-dihydro-1H-indol-1-yl)-2-(dimethylamino)ethan-1-oneYield 69.5%

Reagents, catalysts & solvents 2

HCID 24380Iron chloride (FeCl3)CatalystHCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

A suspension of N,N-dimethyl-2-[5-(methyloxy)-6-nitro-2,3-dihydro-1 H-indol-1-yl]-2-oxoethanamine (26.6 g, 95 mmol), iron(III)chloride (3.09 g, 19.05 mmol), activated carbon (25 g, 95 mmol), and hydrazine hydrate (37.4 mL, 762 mmol) in methanol (500 mL) was warmed to 65° C. and maintained overnight. The reaction was filtered through celite while still warm and all methanol was removed under reduced pressure. The solids were partitioned between ethyl acetate (ca 1 L) and saturated sodium chloride (ca 1 L) and the aqueous layer was washed twice with ethyl acetate (ca 500 mL). The combined organic layers were dried over sodium sulfate, taken to a residue under reduced pressure, and the derived solids triturated with hexanes/diether ether and filtered to afford 1-[(dimethylamino)acetyl]-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine (16.46 g, 69.3% yield) as an off-white solid: NMR: 1H NMR (400 MHz, DMSO-d6) δ ppm 2.23 (s, 6 H), 2.95 (t, J=8.25 Hz, 2 H), 3.11 (s, 2H), 3.69 (s, 3 H), 4.07 (s, 2 H), 4.61 (s, 2 H), 6.68 (s, 1 H), 7.53 (s, 1 H).

Workup

  1. temperaturemaintained overnight
  2. filtrationThe reaction was filtered through celite
  3. temperaturewhile still warm
  4. customall methanol was removed under reduced pressure
  5. customThe solids were partitioned between ethyl acetate (ca 1 L) and saturated sodium chloride (ca 1 L)
  6. washthe aqueous layer was washed twice with ethyl acetate (ca 500 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. customthe derived solids triturated with hexanes/diether ether
  9. filtrationfiltered

Sources & evidence

ORD record
ord-e52e6f4cd60c4ad8b27a9d5c6ddaf426
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Linked notes

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