Triethylamine → 1-[5-(2-Dimethylaminoethanesulfonamido)indole-2-carbonyl]-4-[N-methyl-N-(3-(1-methylethylamino)-2-pyridinyl)amino]piperidine

HRID 1449748Notes

Reaction equation

HRID 1449748 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([N:13]1[CH2:18][CH2:17][CH:16]([N:19]([CH3:30])[C:20]3[C:25]([NH:26][CH:27]([CH3:29])[CH3:28])=[CH:24][CH:23]=[CH:22][N:21]=3)[CH2:15][CH2:14]1)=[O:12])=[CH:5]2.C(N(CC)CC)C.Cl.[CH3:39][N:40]([CH3:47])[CH2:41][CH2:42][S:43](Cl)(=[O:45])=[O:44].S(Cl)(Cl)(=O)=O>C(Cl)Cl.O>[CH3:39][N:40]([CH3:47])[CH2:41][CH2:42][S:43]([NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([N:13]1[CH2:18][CH2:17][CH:16]([N:19]([CH3:30])[C:20]3[C:25]([NH:26][CH:27]([CH3:28])[CH3:29])=[CH:24][CH:23]=[CH:22][N:21]=3)[CH2:15][CH2:14]1)=[O:12])=[CH:5]2)(=[O:45])=[O:44]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 24648Sulfuryl chlorideHCID 142196582-(Dimethylamino)ethane-1-sulfonyl chloride hydrochlorideHCID 153920561-[5-aminoindole-2-carbonyl]-4-[N-methyl-N-(3-(1-methylethylamino)-2-pyridinyl)amino]piperidine

Product 1

HCID 542738891-[5-(2-Dimethylaminoethanesulfonamido)indole-2-carbonyl]-4-[N-methyl-N-(3-(1-methylethylamino)-2-pyridinyl)amino]piperidine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-[5-aminoindole-2-carbonyl]-4-[N-methyl-N-(3-(1-methylethylamino)-2-pyridinyl)amino]piperidine (VII, PREPARATION 56, 400 mg) in dry methylene chloride (5 ml) under nitrogen at 0° is added triethylamine (275 μl) and 2-(dimethylamino)ethanesulfonyl chloride hydrochloride (225 mg). The mixture is stirred at 0° for 1 hr and at 20°-250° for 23 hrs, during which additional sulfonyl chloride (20 mg) and triethylamine (14 μl) are added. The mixture is then diluted with 4 ml of water, the layers are separated, and the organic phase is washed with saline, dried over sodium sulfate and concentrated under reduced pressure to give a solid which is chromatographed on silica gel (70-230 mesh, 46 g), eluting with a gradient of methanol/chloroform (2.5/97.5-6/94). Pooling of fractions having an Rf of 0.36 by TLC (methanol/chloroform, 10/90) and removal of solvent under reduced pressure gives an impure solid. Purification of this solid on two 2000 μ preparative silica gel plates, eluting with methanol/chloroform (10/90) and extracting the appropriate band, gives the title compound, NMR (CDCl3) 10.17, 7.71, 7.55, 7.35, 7.11, 6.94, 6.84, 6.69, 4.63, 4.50, 3.56, 3.45, 3.18, 3.30-3.00, 2.84, 2.63, 2.25, 1.93, 1.65 and 1.22 δ.

Workup

  1. additionare added
  2. customthe layers are separated
  3. washthe organic phase is washed with saline
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto give a solid which
  7. customis chromatographed on silica gel (70-230 mesh, 46 g)
  8. washeluting with a gradient of methanol/chloroform (2.5/97.5-6/94)
  9. customby TLC (methanol/chloroform, 10/90) and removal of solvent under reduced pressure
  10. customgives an impure solid
  11. customPurification of this solid on two 2000 μ preparative silica gel plates
  12. washeluting with methanol/chloroform (10/90)
  13. extractionextracting the appropriate band

Sources & evidence

ORD record
ord-3f8cd528bc304168a00cf2f5af3c8ec4
Source dataset
uspto-grants-1997_02
Patent number
US05599930

Reaction notes

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