Ethanamine, 2-(methylsulfonyl)-, hydrochloride (1:1) → 2-Hydroxy-N-[2-(methylsulfonyl)ethyl]-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxamide hydrochloride

HRID 2245564Notes

Reaction equation

HRID 2245564 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](OC)=[O:25])=[CH:6][CH:5]=2.[ClH:28].[NH2:29][CH2:30][CH2:31][S:32]([CH3:35])(=[O:34])=[O:33]>C(=O)([O-])O.[Na+]>[ClH:28].[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[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)=[CH:13][N:12]=1)=[CH:8][C:7]([C:24]([NH:29][CH2:30][CH2:31][S:32]([CH3:35])(=[O:34])=[O:33])=[O:25])=[CH:6][CH:5]=2

Participants

4

Reactant 2

HCID 17749886Ethanamine, 2-(methylsulfonyl)-, hydrochloride (1:1)HCID 136380045Methyl 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxylate

Product 1

HCID 1354233572-Hydroxy-N-[2-(methylsulfonyl)ethyl]-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carboxamide hydrochlorideYield 36%

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-aminoethylmethylsulfone hydrochloride, but the reaction mixture was after cooling diluted with a saturated sodium hydrogen carbonate solution (10 mL) and concentrated in vacuo. The residue was suspended in methanol/dichloromethane (1:1) and silica gel (˜2 g) was added. 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, (100:10:1), as the eluent to afford the title compound as a base in 36% yield: 1H NMR (DMSO-d6, 300 MHz) δ 14.70 (br s, 1H), 11.42 (br s, 1H), 10.71 (s, 1H), 8.73 (br s, 1H), 8.22 (s, 1H), 8.06 (d, J=9.3 Hz, 1H), 7.99 (s, 1H), 7.82 (d, J=9.3 Hz, 1H), 7.52 (d, J=8.2 Hz, 1H), 6.94 (d, J=8.2 Hz, 1H), 4.25 (s, 2H), 3.98-3.92 (m, 2H), 3.85-3.67 (m, 4H), 3.44-3.29 (m, 4H), 3.12-3.00 (m, 5H); MS (ES) m/z 459 (M++1). The base was converted to the hydrochloride.

Workup

  1. temperatureafter cooling
  2. concentrationconcentrated in vacuo
  3. additionsilica gel (˜2 g) was 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-402a93ef88514f91a123db57d07d86d6
Source dataset
uspto-grants-2010_03
Patent number
US07683067B2

Reaction notes

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