Methanol → 3-[3-(1 H-Indazol-3-yl)-1,2,4-oxadiazol-5-yl]-1-azabicyclo[2.2.2]octane hydrogen oxalate

HRID 2248600Notes

Reaction equation

HRID 2248600 reaction equation
[CH:1]1[CH:6]=[C:5]2[C:7]([NH:12][NH:13][C:4]2=[CH:3][CH:2]=1)=[C:8]([N:10]=[O:11])[NH2:9].[H-].[Na+].[C:16]([CH:20]1[CH:25]2[CH2:26][CH2:27][N:22]([CH2:23][CH2:24]2)[CH2:21]1)([O:18]C)=[O:17].[CH3:28][OH:29]>O1CCCC1>[C:16]([OH:18])(=[O:17])[C:28]([OH:11])=[O:29].[NH:13]1[C:4]2[C:5](=[CH:6][CH:1]=[CH:2][CH:3]=2)[C:7]([C:8]2[N:9]=[C:16]([CH:20]3[CH:25]4[CH2:26][CH2:27][N:22]([CH2:23][CH2:24]4)[CH2:21]3)[O:11][N:10]=2)=[N:12]1

Participants

6

Reactant 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 2736953Methyl quinuclidine-3-carboxylateHCID 178513408HCID 178513408, compound

Product 1

HCID 148108753-[3-(1 H-Indazol-3-yl)-1,2,4-oxadiazol-5-yl]-1-azabicyclo[2.2.2]octane hydrogen oxalate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

[1 H-Indazol-3-yl]amide oxime (190 mg) was dissolved in anhydrous tetrahydrofuran (50 ml) to which was added 4 A molecular sieves. After stirring for 15 minutes sodium hydride (100 mg of 55% dispersion in oil) was added and the mixture stirred for a further 15 minutes before the addition of 3-carbomethoxy-1-azabicyclo[2.2.2]octane (400 mg). The resulting mixture was then heated at reflux for six hours, then cooled to room temperature. Methanol (10 ml) was added, the solution filtered and the solvent evaporated. The residue was purified by chromatography on silica using CH2Cl2 /CH3OH/NH4OH 90/10/1 as eluant to afford a colourless oil (300 mg). This was further purified by treatment with a solution of oxalic acid in acetone to afford the title compound. m.p. 215° C. (dec). Found: C, 58.22; H, 5.44; N, 19.41. C18H17N5O6 requires C, 57.92; H, 5.13; N, 19.30%; δH (360 MHz, D2O) 1.98 (2 H, m, CH2CH2 --N), 2.26 (2 H, m, CH2CH2 --N), 2.75 (1 H, m, CH--CH2CH2 --N), 3.51 (3 H, m, CH2CH2N), 3.97 (3 H, m, CH2CH2N), 7.35 (1 H, t, J=4 Hz, H-6), 7.54 (1 H, t, J=4.9 Hz, H-5), 7.68 (1 H, d, J=4 Hz, H-7), 8.03 (1 H, d, J=4 Hz, H-4); m/z (M+, free base 95%) 295 (95), 238 (15), 212 (100), 159 (40), 143 (35), 96 (70), 83 (60).

Workup

  1. additionwas added 4 A molecular sieves
  2. additionwas added
  3. temperatureThe resulting mixture was then heated
  4. temperatureat reflux for six hours
  5. filtrationthe solution filtered
  6. customthe solvent evaporated
  7. customThe residue was purified by chromatography on silica

Sources & evidence

ORD record
ord-649936f133994218a4130ee379862a37
Source dataset
uspto-grants-1991_08
Patent number
US05041456

Reaction notes

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