Sodium hydride → 1,2,4-Oxadiazole-3-methanamine, 5-[1-(phenylmethyl)-1H-indazol-3-yl]-

HRID 1711611Notes

Reaction equation

HRID 1711611 reaction equation
Cl.[NH2:2][CH2:3][C:4]#[N:5].[Na].Cl.[NH2:8]O.[H-].[Na+].CO[C:14]([C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:17]=1)=[O:15]>CO>[CH2:25]([N:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:16]([C:14]2[O:15][N:8]=[C:4]([CH2:3][NH2:2])[N:5]=2)=[N:17]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 5

HCID 24758Sodium hydrideHCID 443297Hydroxyamine hydrochlorideHCID 5360545Sodium2×HCID 10563690methyl 1-benzyl-1H-indazole-3-carboxylateHCID 11491918Aminoacetonitrile hydrochloride

Product 1

HCID 222390241,2,4-Oxadiazole-3-methanamine, 5-[1-(phenylmethyl)-1H-indazol-3-yl]-Yield 92.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of aminoacetonitrile hydrochloride (0.5 g, 5.4 mmol) and sodium (0.124 g, 5.4 mmol) in MeOH (15 mL) was added to a solution of hydroxylamine hydrochloride (0.37 g, 5.4 mmol) and sodium (0.124 g, 5.4 mmol) in MEOH. The reaction mixture was refluxed for 4 h then filtered and concentrated under reduced pressure. The crude material was taken up in dry THF (30 mL), sodium hydride (0.114 g, 60%, 2.86 mmol) was added and the reaction mixture heated at 60° C. 1-Benzylindazole-3carboxylic acid methyl ester (0.25 g, 0.938 mmol) was added and the reaction mixture was heated at reflux for 4 h. The THF was removed under reduced pressure and the residue partitioned between chloroform (100 mL) and H2O (100 mL). The chloroform layer was separated and the aqueous layer was further extracted with 2×100 mL of chloroform. The combined extracts were dried (MgSO4) and concentrated under reduced pressure. The crude compound was purified by flash chromatography using chloroform/MeOH (95:5) to afford the title compound as a white solid (0.264 g, 92%). Mp 118-119° C. 1H NMR (300 MHz, CDCl3) ppm 1.68 (s, 2H), 4.12 (s, 2H), 5.77 (s, 2H), 7.30-7.47 (m, 8H), 8.32-8.35 (m, 1H). MS(EI) m/z 305 [M+]. Anal. Calcd. for C17H15N5O: C, 66.87; H, 4.95; N, 22.94. Found: C, 67.00; H. 4.82; N, 22.97.

Workup

  1. temperatureThe reaction mixture was refluxed for 4 h
  2. filtrationthen filtered
  3. concentrationconcentrated under reduced pressure
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 4 h
  6. customThe THF was removed under reduced pressure
  7. customthe residue partitioned between chloroform (100 mL) and H2O (100 mL)
  8. customThe chloroform layer was separated
  9. extractionthe aqueous layer was further extracted with 2×100 mL of chloroform
  10. dry with materialThe combined extracts were dried (MgSO4)
  11. concentrationconcentrated under reduced pressure
  12. customThe crude compound was purified by flash chromatography

Sources & evidence

ORD record
ord-1858b2912fba4269bf8a7db21781c771
Source dataset
uspto-grants-2010_09
Patent number
US07790761B2

Reaction notes

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