Potassium Carbonate → HCID 131725178, compound

HRID 966485Notes

Reaction equation

HRID 966485 reaction equation
[CH2:1]([O:8][C:9]([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH2:21][CH2:22][Cl:23])[CH:18]=2)[NH:13][C:12]=1[CH3:24])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:31][N:32]([CH3:38])[CH:33]1[CH2:37][CH2:36][NH:35][CH2:34]1>C(#N)C>[ClH:23].[ClH:23].[CH2:1]([O:8][C:9]([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH2:21][CH2:22][N:35]3[CH2:36][CH2:37][CH:33]([N:32]([CH3:38])[CH3:31])[CH2:34]3)[CH:18]=2)[NH:13][C:12]=1[CH3:24])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27585193-(Dimethylamino)pyrrolidineHCID 23393871HCID 23393871, compound

Product 1

HCID 131725178HCID 131725178, compoundYield 93.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

5-(2-Chloro-ethoxy)-2-methyl-1H-indole-3-carboxylic acid benzyl ester (0.400 g, 1.163 mmol, 1 eq, Example 1, Step A) was suspended in dry acetonitrile (50 mL) under Ar. K2CO3 (0.320 g, 2.32 mmol, 2 eq) and KI (0.020 g, 0.116 mmol, 0.1 eq) were added followed by the addition of 3-(dimethylamino)pyrrolidine (0.198 g, 1.740 mmol, 1.5 eq). The reaction mixture was stirred and heated to reflux for 3 days. 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). 0.270 g (55%) of the indole-pyrrolidine was obtained as a white solid. This was converted to the .2HCl salt. LC/MS (ESI+) 422 (M+1); Anal. Calcd for C25H31N3O3.2HCl.2H2O.0.25AcOEt: C, 56.52; H, 7.11; N, 7.61; Found: C, 56.50; H,. 6.73; N, 7.23.

Workup

  1. temperatureheated
  2. temperatureto reflux for 3 days
  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-7c44ac042ab84ef78152150e4d8af67d
Source dataset
uspto-grants-2005_10
Patent number
US06951848B2

Reaction notes

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