Pyridine → Ethyl 3-[bis(methylsulfonyl)amino]-6-chloro-2-(3-chlorobenzoyl)-1H-indole-1-carboxylate

HRID 651027Notes

Reaction equation

HRID 651027 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([Cl:11])=[CH:8][CH:9]=2)[N:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:3]=1[C:17](=[O:25])[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=1.N1C=CC=CC=1.[CH3:32][S:33](Cl)(=[O:35])=[O:34]>ClCCl>[CH3:32][S:33]([N:1]([S:33]([CH3:32])(=[O:35])=[O:34])[C:2]1[C:10]2[C:5](=[CH:6][C:7]([Cl:11])=[CH:8][CH:9]=2)[N:4]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:3]=1[C:17](=[O:25])[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=1)(=[O:35])=[O:34]

Participants

5

Reactant 3

HCID 1049Pyridine2×HCID 31297Methanesulfonyl chloride2×HCID 183678683-Amino-6-chloro-2-(3-chlorobenzoyl)-1-(ethoxycarbonyl)indole

Product 1

HCID 21710894Ethyl 3-[bis(methylsulfonyl)amino]-6-chloro-2-(3-chlorobenzoyl)-1H-indole-1-carboxylateYield 98.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of ethyl 3-amino-6-chloro-2-(3-chlorobenzoyl)-]-1H-indole-1-carboxylate (step 1 of Example 4, 507 mg, 1.25 mmol) in dichloromethane (15 ml) was added pyridine (0.32 ml, 4.04 mmol) and methanesulfonyl chloride (0.16 ml, 2.02 mmol). After stirring for 19 h, additional pyridine (1.3 ml, 16.2 mmol) and methanesulfonyl chloride (0.32 ml, 4.04 mmol) were added and the mixture heated at reflux for 17 h and then cooled to room temperature. The mixture was concentrated, and partitioned between ethyl acetate (200 ml) and 2 M aqueous HCl (100 ml). The organic layer was separated and washed with 2 M aqueous HCl (100 ml×2), saturated aqueous sodium bicarbonate (100 ml×3), and dried (Na2SO4). After removal of solvent the residue was purified by flash chromatography eluting with ethyl acetate/hexane (1:4) to afford the title compound (532 mg, 74%) as an oil.

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 17 h
  3. concentrationThe mixture was concentrated
  4. custompartitioned between ethyl acetate (200 ml) and 2 M aqueous HCl (100 ml)
  5. customThe organic layer was separated
  6. washwashed with 2 M aqueous HCl (100 ml×2), saturated aqueous sodium bicarbonate (100 ml×3)
  7. dry with materialdried (Na2SO4)
  8. customAfter removal of solvent the residue
  9. customwas purified by flash chromatography
  10. washeluting with ethyl acetate/hexane (1:4)

Sources & evidence

ORD record
ord-9f5249de2f8249f881b9dd1a8550f1b2
Source dataset
uspto-grants-2001_08
Patent number
US06277878B1

Reaction notes

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