Sodium hydride → 9-(3,5-dinitrobenzyl)-3-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]-9H-beta-carboline

HRID 992567Notes

Reaction equation

HRID 992567 reaction equation
[CH3:1][O:2][CH2:3][C:4](=[N:6][OH:7])[NH2:5].[H-].[Na+].[N+:10]([C:13]1[CH:14]=[C:15]([CH:34]=[C:35]([N+:37]([O-:39])=[O:38])[CH:36]=1)[CH2:16][N:17]1[C:29]2[CH:28]=[N:27][C:26]([C:30](OC)=O)=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[CH:21][CH:22]=2)([O-:12])=[O:11]>O1CCCC1>[N+:10]([C:13]1[CH:14]=[C:15]([CH:34]=[C:35]([N+:37]([O-:39])=[O:38])[CH:36]=1)[CH2:16][N:17]1[C:29]2[CH:28]=[N:27][C:26]([C:30]3[O:7][N:6]=[C:4]([CH2:3][O:2][CH3:1])[N:5]=3)=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[CH:21][CH:22]=2)([O-:12])=[O:11]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 4126736N'-hydroxy-2-methoxyethanimidamideHCID 18412208HCID 18412208, compound

Product 1

HCID 184122199-(3,5-dinitrobenzyl)-3-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]-9H-beta-carbolineYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of 2-methoxyacetamidoxime (260 mg, 2.5 mmol) and 4 Å molecular sieves (1 g) in anhydrous tetrahydrofuran (15 mL) was stirred at room temperature for 0.5 hours, then treated with sodium hydride (2.75 mmol, 110 mg of 60% mineral oil suspension). The mixture was heated at reflux for 1 hour. After cooling to room temperature, a suspension of methyl 9-(3,5-dinitrobenzyl)-9H-β-carboline-3-carboxylate (205 mg, 0.5 mmol) in anhydrous tetrahydrofuran (10 mL) was added. The resulting mixture was heated at reflux for 15 hours, cooled, filtered, and the filtrate concentrated in vacuo. The residue was purified by preparative thin layer chromatography with 4% 2M NH3—CH3OH in CH2Cl2 as eluent to afford the desired product (86 mg, 38% yield) as a white solid. 1H NMR (DMSO-d6) δ9.41 (s, 1H), 9.24 (s, 1H), 8.72 (t, J=1.9 Hz, 1H), 8.59 (d, J=7.8, 1H), 8.49 (d, J=1.9 Hz, 2H), 7.94 (d, J=8.3 Hz, 1H), 7.73 (t, J=7.8Hz, 1H), 7.45 (t, J=7.5 Hz, 1H), 6.20 (s, 2H), 4.67 (s, 2H), 3.42 (s, 3H); MS (APCI; (M+H)+) m/z 461.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 1 hour
  3. temperatureAfter cooling to room temperature
  4. additionwas added
  5. temperatureThe resulting mixture was heated
  6. temperatureat reflux for 15 hours
  7. temperaturecooled
  8. filtrationfiltered
  9. concentrationthe filtrate concentrated in vacuo
  10. customThe residue was purified by preparative thin layer chromatography with 4% 2M NH3—CH3OH in CH2Cl2 as eluent

Sources & evidence

ORD record
ord-c4ae2c1ef24c4156b4d61a9467f3df41
Source dataset
uspto-grants-2002_10
Patent number
US06469021B1

Reaction notes

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