Imidazole → HCID 69943613, compound

HRID 566469Notes

Reaction equation

HRID 566469 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:42])[CH:10]=[C:11]2[NH:15][C:14]([CH2:23][CH2:24]OS(C)(=O)=O)([CH2:16][C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[C:13](=[O:30])[N:12]2[CH2:31][CH:32]2[CH2:37][CH:36]3[CH2:38][CH:34]([C:35]3([CH3:40])[CH3:39])[CH:33]2[CH3:41])=[CH:5][CH:4]=1)#[N:2].[NH:43]1[CH:47]=[CH:46][N:45]=[CH:44]1.C([O-])([O-])=O.[K+].[K+]>CN(C)C=O>[N:43]1([CH2:24][CH2:23][C:14]2([CH2:16][C:17]3[CH:18]=[CH:19][N:20]=[CH:21][CH:22]=3)[C:13](=[O:30])[N:12]([CH2:31][CH:32]3[CH2:37][CH:36]4[CH2:38][CH:34]([C:35]4([CH3:39])[CH3:40])[CH:33]3[CH3:41])[C:11](=[CH:10][C:9]([C:6]3[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=3)=[O:42])[NH:15]2)[CH:47]=[CH:46][N:45]=[CH:44]1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 86755484HCID 86755484, compound

Product 1

HCID 69943613HCID 69943613, compoundYield 66.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Methanesulfonic acid 2-[2-[2-(4-cyano-phenyl)-2-oxo-ethylidene]-5-oxo-4-pyridin-4-ylmethyl-1-((+)-(2,6,6-trimethyl-bicyclo[3.1.1]hept-3-ylmethyl))-imidazolidin-4-yl]-ethyl ester (300 mg, 0.508 mMol) and imidazole (102 mg, 1.5 mMol) were dissolved in anhydrous dimethylformamide (2 mL) under an atmosphere of dry N2. To this mixture was added K2CO3 (207 mg, 1.5 mMol). The mixture was heated to 80° C. for 24 hours after which time it was cooled to ambient temperature and subsequently concentrated under vacuum. The residue was partitioned between CH2Cl2 and water. The CH2Cl2 layer was dried over Na2SO4, filtered and concentrated under vacuum to give a foam. The foam was chromatographed on flash silica gel using a gradient of CHCl3—CH3OH (98:2) to CHCl3—CH3OH (96:4) to give 190 mg of the titled compound as a 1:1 mixture of diastereomers: C.I. m/z 563.4 [M+1]; 1H NMR (CDCl3)δ8.42 (m, 4H), 7.86 (m, 4H), 7.74 (m, 4H), 7.38 (s, 1H), 7.31 (s, 1H), 7.06 (m, 4H), 7.04 (s, 1 H), 7.02 (s, 1H), 6.88 (s, 1H), 6.84 (s, 1H), 5.50 (s, 1H), 5.45 (s, 1H), 3.80-4.10 (m, 4H), 2.90-3.35 (m, 8H), 2.60 (m 2H), 2.26 (m, 4H), 1.20-2.00 (m, 14H), 1.15 (s, 3H), 1.14 (s, 3H), 1.04 (m, 6H), 0.90 (s, 3H), 0.84 (s, 3H).

Workup

  1. temperaturewas cooled to ambient temperature
  2. concentrationsubsequently concentrated under vacuum
  3. customThe residue was partitioned between CH2Cl2 and water
  4. dry with materialThe CH2Cl2 layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customto give a foam
  8. customThe foam was chromatographed on flash silica gel using a gradient of CHCl3—CH3OH (98:2) to CHCl3—CH3OH (96:4)

Sources & evidence

ORD record
ord-ca88b36eb2e1420ebe1e7c6edd581671
Source dataset
uspto-grants-2001_01
Patent number
US06174903B1

Reaction notes

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