2-Aminoethanesulphonamide monohydrochloride → N-[2-(Aminosulfonyl)ethyl]-2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxamide hydrochloride

HRID 2245563Notes

Reaction equation

HRID 2245563 reaction equation
[OH:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:13][N:12]=1)=[CH:8][C:7]([C:24]([O:26]C)=O)=[CH:6][CH:5]=2.[ClH:28].[NH2:29][CH2:30][CH2:31][S:32]([NH2:35])(=[O:34])=[O:33].C[Al](C)C>C(=O)([O-])O.[Na+]>[ClH:28].[NH2:35][S:32]([CH2:31][CH2:30][NH:29][C:24]([C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[NH:3][C:2]([OH:1])=[C:10]2[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][N:18]2[CH2:19][CH2:20][O:21][CH2:22][CH2:23]2)=[CH:13][N:12]=1)=[O:26])(=[O:34])=[O:33]

Participants

5

Reactant 3

HCID 30215492-Aminoethanesulphonamide monohydrochlorideHCID 16682925TrimethylaluminumHCID 136380045Methyl 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxylate

Product 1

HCID 135405910N-[2-(Aminosulfonyl)ethyl]-2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxamide hydrochlorideYield 40%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

Starting materials: methyl 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxylate and 2-aminoethanesulfonamide hydrochloride, but the reaction mixture was heated at 80° C. for 22 h. After the first 2 h, an additional 6 eqv. of trimethylaluminium was added to the reaction mixture. The mixture was cooled, diluted with a saturated sodium hydrogen carbonate solution (10 mL) and concentrated in vacuo. The residue was suspended in methanol/dichloromethane, (1:1), silica gel (˜2 g) was added and the mixture was re-concentrated in vacuo, resulting in a fine yellow powder that was purified on a silica gel column using dichloromethane/methanol/aqueous NH3, (first 100:10:1, then 70:10:1), as the eluent to afford the title compound as a base in 40% yield: 1H NMR (DMSO-d6, 300 MHz) δ 14.5 (br s, 1H), 11.29 (br s, 1H), 10.69 (s, 1H), 8.61 (br s, 1H), 8.22 (s, 1H), 8.04 (d, J=9.0 Hz, 1H), 7.98 (s, 1H), 7.82 (d, J=9.0 Hz, 1H), 7.51 (d, J=8.2 Hz, 1H), 6.96-6.90 (m, 3H), 4.25 (s, 2H), 3.98-3.64 (m, 14H), 3.36-3.22 (m, 4H), 3.12-3.04 (m, 2H); MS (ES) m/z 460 (M++1). The base was converted to the hydrochloride

Workup

  1. temperatureThe mixture was cooled
  2. concentrationconcentrated in vacuo
  3. additionwas added
  4. concentrationthe mixture was re-concentrated in vacuo
  5. customresulting in a fine yellow powder that
  6. customwas purified on a silica gel column

Sources & evidence

ORD record
ord-1da330568e6e4c00bcd97839b252da12
Source dataset
uspto-grants-2010_03
Patent number
US07683067B2

Reaction notes

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