Methanol → HCID 135496240, compound

HRID 2245558Notes

Reaction equation

HRID 2245558 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]([NH:25][CH2:26][CH2:27][N:28]2[CH2:32][CH2:31][CH2:30][CH2:29]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1.CO>CN1CCCC1=O>[ClH:15].[C:13]([C:8]1[CH:7]=[C:6]2[C:11]([C:12]([C:16]3[N:21]=[CH:20][C:19]([S:22]([NH:25][CH2:26][CH2:27][N:28]4[CH2:32][CH2:31][CH2:30][CH2:29]4)(=[O:24])=[O:23])=[CH:18][CH:17]=3)=[C:4]([OH:3])[NH:5]2)=[CH:10][CH:9]=1)#[N:14]

Participants

6

Reactant 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 27733482-Oxindole-6-carbonitrileHCID 11162077HCID 11162077, compound

Product 1

HCID 135496240HCID 135496240, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a suspension of sodium hydride (97%, 0.036 g, 1.5 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 6-chloro-N-(2-pyrrolidin-1-ylethyl)pyridine-3-sulfonamide (0.145 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 (0.4 mL) was added and the solvents were removed in vacuo. The crude product was purified by preparative HPLC purification (XTerra®PrepMS C8 column 10 μm, 30×150 mm; 0.1 M NH4OAc buffer/acetonitrile, (80:20 to 40:60), as a eluent gradient). The collected product was stirred for 16 h in methanol/ethyl acetate, (5:1 mL), and the brownish red solid was collected by filtration affording 0.056 g (27% yield) of the title compound as the base. The base (0.046 g, 0.11 mmol) was dissolved in chloroform/methanol, (1:1), and treated with HCl in diethyl ether (1 M) at 0° C. The resulting brownish red crystals were collected by filtration and washed with diethyl ether to obtain 0.022 g (40% yield) of the title compound: 1H NMR (D2O, 400 MHz) δ 8.63 (s, 1H), 8.10 (d, J=9.2 Hz, 1H), 7.99 (d, J=8.4 Hz, 1H), 7.80 (dd, J=9.2, 2.4 Hz, 1H), 7.22 (s, 1H), 7.21 (dd, J=8.0, 1.6 Hz, 1H) 2.91 (t, J=6.8 Hz, 2H), 2.51 (m, 6H), 1.61 (br s, 4H); MS (EI) m/z 412 (M++1).

Workup

  1. customThe resulting reaction mixture
  2. stirringstirred for 1 h at 90° C
  3. customthe solvents were removed in vacuo
  4. customThe crude product was purified by preparative HPLC purification (XTerra®PrepMS C8 column 10 μm, 30×150 mm
  5. stirringThe collected product was stirred for 16 h in methanol/ethyl acetate, (5:1 mL),
  6. filtrationthe brownish red solid was collected by filtration

Sources & evidence

ORD record
ord-b803ec86bca54dda988434903fa94536
Source dataset
uspto-grants-2010_03
Patent number
US07683067B2

Reaction notes

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