Sodium hydride → HCID 59199451, compound

HRID 2089542Notes

Reaction equation

HRID 2089542 reaction equation
[OH:1][NH:2][C:3](=[NH:5])[CH3:4].[H-].[Na+].CO[C:10]([C:12]1[N:13]([CH:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:19][C:18]2([CH3:27])[CH3:26])[CH:14]=[N:15][CH:16]=1)=O>C1COCC1>[CH3:26][C:18]1([CH3:27])[CH2:19][C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:17]1[N:13]1[C:12]([C:10]2[O:1][N:2]=[C:3]([CH3:4])[N:5]=2)=[CH:16][N:15]=[CH:14]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 218730963-(2,2-dimethyl-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl esterHCID 178465666HCID 178465666, compound

Product 1

HCID 59199451HCID 59199451, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution N-hydroxy-acetamidine (137 mg, 1.85 mmol) in THF (5 mL) is added 4 angstrom molecular sieves (500 mg) followed by a 60% oil dispersion of NaH (80 mg, 2.0 mmol). The heterogeneous mixture is heated at 60° C. for 1 hour at which time a solution of 3-(2,2-dimethyl-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester, which can be prepared as described in Example 10, (200 mg, 0.74 mmol) in THF (5 mL) is added. The reaction is heated at reflux for 1.5 hours, at which time the reaction is cooled to 0° C. and quenched with water. The reaction is diluted with dichloromethane and filtered. The layers are separated and the aqueous layer is extracted three times with dichloromethane. The organic layers are combined, dried with Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:9) to afford 5-[3-(2,2-Dimethyl-indan-1-yl)-3H-imidazol-4-yl]-3-methyl-[1,2,4]oxadiazole; HRMS: (ESI) m/z 259.1566 [(M+H)+: Calcd for C17H19N4O: 295.1559]; 1H NMR (400 MHz, CDCl3) δ ppm 0.75 (s, 3 H), 1.27 (s, 3 H), 2.50 (s, 3 H), 2.71-3.10 (m, 2 H), 6.37 (s, 1 H), 7.17 (s, 1 H), 7.23-7.43 (m, 4 H), 7.98 (s, 1 H).

Workup

  1. customcan be prepared
  2. additionis added
  3. temperatureThe reaction is heated
  4. temperatureat reflux for 1.5 hours, at which time the reaction
  5. customquenched with water
  6. additionThe reaction is diluted with dichloromethane
  7. filtrationfiltered
  8. customThe layers are separated
  9. extractionthe aqueous layer is extracted three times with dichloromethane
  10. dry with materialdried with Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:9)

Sources & evidence

ORD record
ord-9c50d90be2bc4d1cabb43ed75f948db4
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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