Diisopropylethylamine → n-((Dimethylamino)acetyl)-1-methyl-n-(3,4,5-trimethoxyphenyl)-1h-indole-5-sulfonamide

HRID 50122Notes

Reaction equation

HRID 50122 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([S:11]([NH:14][C:15]3[CH:20]=[C:19]([O:21][CH3:22])[C:18]([O:23][CH3:24])=[C:17]([O:25][CH3:26])[CH:16]=3)(=[O:13])=[O:12])=[CH:8][CH:9]=2)[CH:4]=[CH:3]1.Cl.[CH3:28][N:29]([CH2:31][C:32](Cl)=[O:33])[CH3:30].C(N(C(C)C)CC)(C)C>C1COCC1.CN(C1C=CN=CC=1)C>[CH3:28][N:29]([CH2:31][C:32]([N:14]([C:15]1[CH:16]=[C:17]([O:25][CH3:26])[C:18]([O:23][CH3:24])=[C:19]([O:21][CH3:22])[CH:20]=1)[S:11]([C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[N:2]([CH3:1])[CH:3]=[CH:4]2)(=[O:13])=[O:12])=[O:33])[CH3:30]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 99295711-methyl-N-(3,4,5-trimethoxyphenyl)-1H-indole-5-sulfonamideHCID 139949912-(Dimethylamino)acetyl chloride hydrochloride

Product 1

HCID 9955950n-((Dimethylamino)acetyl)-1-methyl-n-(3,4,5-trimethoxyphenyl)-1h-indole-5-sulfonamideYield 92%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of Example 4 (20.0 g, 53.2 mmol) in THF (250 mL) at room temperature was treated with dimethylaminoacetyl chloride hydrochloride (12.3 g, 77.8 mmol), DMAP (650 mg, 5.3 mmol), and diisopropylethylamine (25.2 g, 195.0 mmol), stirred for 8 hours, and concentrated to ⅓ its original volume. The mixture was diluted with ethyl acetate (400 mL), washed with 5% NaHCO3 (2×200 mL) and water (200 mL), dried (Na2SO4), filtered, concentrated to a volume of 120 mL, diluted with methyl tert-butyl ether (120 mL), stirred for 18 hours, cooled to 0° C., stirred for 2 hours, and filtered. The resulting solid was washed with 1:1 ethyl acetate/methyl tert-butyl ether (100 mL) and dried under vacuum to provide 22.5 g (92%) of the desired product.

Workup

  1. concentrationconcentrated
  2. additionThe mixture was diluted with ethyl acetate (400 mL)
  3. washwashed with 5% NaHCO3 (2×200 mL) and water (200 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated to a volume of 120 mL
  7. additiondiluted with methyl tert-butyl ether (120 mL)
  8. stirringstirred for 18 hours
  9. stirringstirred for 2 hours
  10. filtrationfiltered
  11. washThe resulting solid was washed with 1:1 ethyl acetate/methyl tert-butyl ether (100 mL)
  12. customdried under vacuum

Sources & evidence

ORD record
ord-00d084a0718e4d45adc6d05b8ef4d1b0
Source dataset
uspto-grants-2004_03
Patent number
US06710185B2

Reaction notes

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