3-(N-Acetyl-N-methylamino)pyrrolidine → 1H-Indolamine

HRID 966494Notes

Reaction equation

HRID 966494 reaction equation
C(OC([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17](CCOS(C)(=O)=O)[CH:18]=2)[NH:13][C:12]=1C)=O)C1C=CC=CC=1.C([N:31](C1CCNC1)C)(=O)C>O1CCOCC1>[NH:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:11]=[C:12]1[NH2:31]

Participants

4

Reactant 2

HCID 130411303-(N-Acetyl-N-methylamino)pyrrolidineHCID 233938525-(2-Methanesulfonyloxy-ethyl)-2-methyl-1H-indole-3-carboxylic Acid Benzyl Ester

Product 1

HCID 1220741H-IndolamineYield 196.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

5-(2-Methanesulfonyloxy-ethyl)-2-methyl-1H-indole-3-carboxylic acid benzyl ester (0.300 g, 0.770 mmol, 1 eq, Example 56, Step D) was suspended in Dioxane (20 mL) under Ar. 3-(N-Acetyl-N-methylamino)-pyrrolidine (0.330 g, 2.320 mmol, 3 eq) was added. The reaction mixture was stirred and heated to reflux for 18 hours. Then the reaction was quenched with saturated sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic phases were washed with brine and dried over Na2SO4. After removing the solvent, the residue was loaded on silica gel and chromatographed, eluting with ethyl acetate/methanol/triethyl amine (100/10/1). 0.200 g (60%) of the indole-amine was obtained as a white solid. This was converted to the .HCl salt. LC/MS (ESI+) 434 (M+1); Anal. Calcd for C26H31N3O3.1HCl.1.25H2O: C, 63.40; H, 7.06; N, 8.53; Found: C, 63.51; H, 6.95; N, 8.30.

Workup

  1. temperatureheated
  2. temperatureto reflux for 18 hours
  3. customThen the reaction was quenched with saturated sodium bicarbonate
  4. extractionextracted with ethyl acetate (3×)
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over Na2SO4
  7. customAfter removing the solvent
  8. customchromatographed
  9. washeluting with ethyl acetate/methanol/triethyl amine (100/10/1)

Sources & evidence

ORD record
ord-2c4fcf99f5d34a43970078141d918f31
Source dataset
uspto-grants-2005_10
Patent number
US06951848B2

Reaction notes

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