Hydrochloric Acid → 2-Hydroxy-3-[5-(piperazine-1-sulfonyl)pyridin-2-yl]-1H-indole-6-carbonitrile hydrochloride

HRID 2245559Notes

Reaction equation

HRID 2245559 reaction equation
[H-].[Na+].[O:3]=[C:4]1[CH2:12][C:11]2[C:6](=[CH:7][C:8]([C:13]#[N:14])=[CH:9][CH:10]=2)[NH:5]1.[Cl:15][C:16]1[N:21]=[CH:20][C:19]([S:22]([N:25]2[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1.Cl.C(OCC)C>CN1CCCC1=O.CO>[ClH:15].[OH:3][C:4]1[NH:5][C:6]2[C:11]([C:12]=1[C:16]1[CH:17]=[CH:18][C:19]([S:22]([N:25]3[CH2:26][CH2:27][NH:28][CH2:29][CH2:30]3)(=[O:24])=[O:23])=[CH:20][N:21]=1)=[CH:10][CH:9]=[C:8]([C:13]#[N:14])[CH:7]=2

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 24758Sodium hydrideHCID 27733482-Oxindole-6-carbonitrileHCID 11739940Tert-butyl 4-(6-chloropyridin-3-ylsulfonyl)piperazine-1-carboxylate

Product 1

HCID 1354316282-Hydroxy-3-[5-(piperazine-1-sulfonyl)pyridin-2-yl]-1H-indole-6-carbonitrile hydrochlorideYield 99.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a suspension of sodium hydride (97%, 0.024 g, 1.0 mmol) in 1-methyl-2-pyrrolidinone (2 mL) was added 2-oxoindoline-6-carbonitrile (0.119 g, 0.75 mmol). The formed mixture was stirred for 5 min at room temperature and tert-butyl 4-[(6-chloropyridin-3-yl)sulfonyl]piperazine-1-carboxylate (0.181 g, 0.5 mmol) was added. The resulting reaction mixture was set under an N2 atmosphere and stirred for 1 h at 90° C. Methanol (0.5 mL) was added to the mixture and the solvents were removed in vacuo. The crude product was dissolved in methanol (5 mL) and HCl in diethyl ether (4 M, 2.5 mL, 10 mmol) was added followed by reflux for 3 h. From the cooled solution the formed yellow precipitate was collected by filtration and dried to give 0.209 g (92% yield) of the title compound: 1H NMR (DMSO-d6, 400 MHz) δ 11.08 (s, 1H), 9.10 (br s, 2H), 8.67 (s, 1H), 7.89 (s, 2H), 7.78 (d, J=8.0 Hz, 1H), 7.44 (dd, J=8.0, 1.2 Hz, 1H), 7.28 (d, J=1.2 Hz, 1H) 3.31 (br s, 4H), 3.25 (br s, 4H); MS (EI) m/z 384 (M++1).

Workup

  1. customThe resulting reaction mixture
  2. stirringstirred for 1 h at 90° C
  3. customthe solvents were removed in vacuo
  4. dissolutionThe crude product was dissolved in methanol (5 mL)
  5. temperatureby reflux for 3 h
  6. filtrationFrom the cooled solution the formed yellow precipitate was collected by filtration
  7. customdried

Sources & evidence

ORD record
ord-a242f4906fdb467fb13e747373597e88
Source dataset
uspto-grants-2010_03
Patent number
US07683067B2

Reaction notes

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