Bis-(1H-imidazol-2-YL)-methanone → HCID 136338592, compound

HRID 1297244Notes

Reaction equation

HRID 1297244 reaction equation
[C:1]([O:5][C:6](=[O:20])[NH:7][CH2:8][C:9]1([C:16](=[NH:19])[NH:17][OH:18])[CH2:11][CH:10]1[CH2:12][CH:13]([CH3:15])[CH3:14])([CH3:4])([CH3:3])[CH3:2].[C:21](C1NC=CN=1)(C1NC=CN=1)=[O:22]>C1COCC1>[C:1]([O:5][C:6](=[O:20])[NH:7][CH2:8][C:9]1([C:16]2[NH:19][C:21](=[O:22])[O:18][N:17]=2)[CH2:11][CH:10]1[CH2:12][CH:13]([CH3:14])[CH3:15])([CH3:3])([CH3:4])[CH3:2]

Participants

4

Reactant 2

HCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 178440561HCID 178440561, compound

Product 1

HCID 136338592HCID 136338592, compoundYield 76.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of [1-(N-hydroxycarbamimidoyl)-2-isobutyl-cyclopropylmethyl]-carbamic acid tert-butyl ester (5.6 g, 19.6 mmol) in dry THF (190 mL) was added dropwise a solution of carbonyl diimidazole (4.8 g, 29.4 mmol) in dry THF (190 mL). The reaction mixture was heated to reflux for 12 hours and allowed to cool to room temperature. Excess of solvents was removed in vacuo and the residue was partitioned between ether (100 mL) and 1N NaOH (100 mL) solution. The ethereal solution was extracted with 1N NaOH (2×50 mL) and the combined aqueous layers were acidified to pH=3 with 4N HCl solution. The aqueous solution was extracted with EtOAc (3×100 mL) and the combined organic phase was washed with brine and dried over Na2SO4. Removal of excess of solvent, followed by purification of the residue by flash column chromatography using hexanes/EtOAc (1:1) as an eluent gave 4.66 g (76%) of {2-isobutyl-1-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-cyclopropylmethyl}-carbamic acid tert-butyl ester as a colorless foam: 1H NMR (300 MHz, CD3OD) δ 0.89 (t, J=5.7 Hz, 1H), 0.96 (d, J=5.1 Hz, 3H), 0.98 (d, J=5.1 Hz, 3H), 1.26-1.37 (m, 3H), 1.43 (s, 9H), 1.63-1.71 (m, 2H), 3.35 (d, J=14.8 Hz, 1H), 3.53 (d, J=14.8 Hz, 1H); MS (APCI) m/z 210 [M+H-100(Boc)]+.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 12 hours
  3. customExcess of solvents was removed in vacuo
  4. customthe residue was partitioned between ether (100 mL) and 1N NaOH (100 mL) solution
  5. extractionThe ethereal solution was extracted with 1N NaOH (2×50 mL)
  6. extractionThe aqueous solution was extracted with EtOAc (3×100 mL)
  7. washthe combined organic phase was washed with brine
  8. dry with materialdried over Na2SO4
  9. customRemoval of excess of solvent
  10. customfollowed by purification of the residue by flash column chromatography

Sources & evidence

ORD record
ord-9ecaffe012e5436f818c2da09b7f34bc
Source dataset
uspto-grants-2007_07
Patent number
US07250433B2

Reaction notes

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