Methanesulfonamide → N-Methanesulfonyl-6-(6-methoxy-2-thiophen-3-yl-1H-indol-3-ylmethyl)pyridine-2-carboxamide

HRID 2409970Notes

Reaction equation

HRID 2409970 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH2:17][C:18]3[N:23]=[C:22]([C:24](O)=[O:25])[CH:21]=[CH:20][CH:19]=3)=[C:8]([C:12]3[CH:16]=[CH:15][S:14][CH:13]=3)[NH:9]2)=[CH:5][CH:4]=1.[CH3:27][S:28]([NH2:31])(=[O:30])=[O:29].Cl.C(N=C=NCCCN(C)C)C>ClCCl.CN(C)C1C=CN=CC=1>[CH3:27][S:28]([NH:31][C:24]([C:22]1[CH:21]=[CH:20][CH:19]=[C:18]([CH2:17][C:7]2[C:6]3[C:10](=[CH:11][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[NH:9][C:8]=2[C:12]2[CH:16]=[CH:15][S:14][CH:13]=2)[N:23]=1)=[O:25])(=[O:30])=[O:29]

Participants

6

Reactant 3

HCID 72879MethanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 509020026-(6-Methoxy-2-thiophen-3-yl-1H-indol-3-ylmethyl)pyridine-2-carboxylic acid

Product 1

HCID 68184622N-Methanesulfonyl-6-(6-methoxy-2-thiophen-3-yl-1H-indol-3-ylmethyl)pyridine-2-carboxamideYield 39.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Under an argon atmosphere, to a suspension of 6-(6-methoxy-2-thiophen-3-yl-1H-indol-3-ylmethyl)pyridine-2-carboxylic acid (45.5 mg) in dichloromethane (0.6 mL) were added methane sulfonamide (11.9 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (23.9 mg), and 4-dimethylaminopyridine (15.3 mg), and this mixture was stirred at room temperature for 2 days. The reaction mixture was concentrated under reduced pressure. To the residue was added 10% aqueous citric acid solution, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine successively, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. To the residue was added ethanol, and this suspension was heated to reflux for 45 minutes to give a solution. This solution was left to be cooled. The precipitate was collected by filtration and dried under reduced pressure to obtain the title compound (21.9 mg). 1H-NMR (DMSO-d6) δ ppm: 3.38 (3H, s), 3.77 (3H, s), 4.47 (2H, s), 6.65 (1H, dd, J=2.3, 8.6 Hz), 6.85 (1H, d, J=2.3 Hz), 7.27-7.35 (1H, m), 7.42 (1H, d, J=8.6 Hz), 7.56 (1H, dd, J=1.3, 5.0 Hz), 7.67 (1H, dd, J=3.0, 5.0 Hz), 7.81-7.91 (3H, m), 11.17 (1H, s), 11.42-11.66 (1H, br).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionTo the residue was added 10% aqueous citric acid solution
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine successively
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. additionTo the residue was added ethanol
  8. temperaturethis suspension was heated
  9. temperatureto reflux for 45 minutes
  10. customto give a solution
  11. waitThis solution was left
  12. temperatureto be cooled
  13. filtrationThe precipitate was collected by filtration
  14. customdried under reduced pressure

Sources & evidence

ORD record
ord-a792896a59344600a00b12620d025724
Source dataset
uspto-grants-2014_08
Patent number
US08815903B2

Reaction notes

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