Sodium hydride → HCID 178509468, compound

HRID 2245576Notes

Reaction equation

HRID 2245576 reaction equation
[O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[CH:5][C:6]([C:11]#[N:12])=[CH:7][CH:8]=2)[NH:3]1.Cl[C:14]1[N+:19]([O-:20])=[CH:18][C:17]([CH2:21][N:22]2[CH2:27][CH2:26][NH:25][C:24](=[O:28])[CH2:23]2)=[CH:16][CH:15]=1.[H-].[Na+]>CN1CCCC1=O>[OH:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[C:14]1[CH:15]=[CH:16][C:17]([CH2:21][N:22]3[CH2:27][CH2:26][NH:25][C:24](=[O:28])[CH2:23]3)=[CH:18][N+:19]=1[O-:20])=[CH:8][CH:7]=[C:6]([C:11]#[N:12])[CH:5]=2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27733482-Oxindole-6-carbonitrileHCID 86038280HCID 86038280, compound

Product 1

HCID 178509468HCID 178509468, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

2-Oxoindoline-6-carbonitrile (0.063 g, 0.397 mmol) was added to a suspension of 4-[(6-chloro-1-oxidopyridin-3-yl)methyl]piperazin-2-one (0.080 g, 0.33 mmol) and sodium hydride (0.042 g, 1.75 mmol) in 1-methyl-2-pyrrolidone (3 mL). The mixture was stirred at room temperature for 10 min, heated at 90° C. for 1 h and finally quenched with methanol (0.5 mL). Trituration with acetonitrile and drying in vacuo gave the crude 2-hydroxy-3-{1-oxido-5-[(3-oxopiperazin-1-yl)methyl]pyridin-2-yl}-1H-indole-6-carbonitrile as a solid. The crude intermediate was suspended in chloroform (5 mL) and phosphorus trichloride (0.5 mL, 5.73 mmol) was added. The mixture was stirred at 60° C. for 3 h and then concentrated in vacuo. Purification using preparative HPLC (XTerra®PrepMS C8 column 10 μm, 30×150 mm; 0.1 M NH4OAc buffer/acetonitrile, (80:20-20:80), as the eluent) gave a yellow solid that was dissolved in dichloromethane/methanol, (9:1), and treated with HCl in diethyl ether (1 M) at 0° C. The resulting yellow crystals were collected by filtration, washed with diethyl ether, and dried to obtain 0.036 g (26% yield) of the title compound: 1H NMR (D2O, 400 MHz) 8.16 (d, J=2 Hz, 1H), 7.96 (dd, J=9, 2 Hz, 1H), 7.80 (d, J=9 Hz, 1H), 7.61 (d, J=8 Hz, 1H), 7.35 (dd, J=8, 1 Hz, 1H), 7.31 (s, 1H), 4.11 (s, 2H), 3.62 (s, 2H), 3.51 (t, J=5H, 2H); MS (ESP) m/z 348 (M++1).

Workup

  1. temperatureheated at 90° C. for 1 h
  2. customfinally quenched with methanol (0.5 mL)
  3. dry with materialTrituration with acetonitrile and drying in vacuo

Sources & evidence

ORD record
ord-12351662205d449fa214fe8fcda34add
Source dataset
uspto-grants-2010_03
Patent number
US07683067B2

Reaction notes

Loading…