Water → HCID 67225677, compound

HRID 1966799Notes

Reaction equation

HRID 1966799 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:32]=[CH:31][C:11]3[N:12]([C:27]([CH3:30])([CH3:29])[CH3:28])[C:13]([C:15]4[CH:16]=[C:17]([OH:26])[CH:18]=[CH:19][C:20]=4[N:21]4[CH:25]=[N:24][CH:23]=[N:22]4)=[N:14][C:10]=3[CH:9]=2)=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH:39]([N:42]=[C:43]=[O:44])([CH3:41])[CH3:40].O>C1COCC1>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:8]2[CH:32]=[CH:31][C:11]3[N:12]([C:27]([CH3:29])([CH3:28])[CH3:30])[C:13]([C:15]4[CH:16]=[C:17]([O:26][C:43](=[O:44])[NH:42][CH:39]([CH3:41])[CH3:40])[CH:18]=[CH:19][C:20]=4[N:21]4[CH:25]=[N:24][CH:23]=[N:22]4)=[N:14][C:10]=3[CH:9]=2)=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 61277Isopropyl isocyanateHCID 58542027HCID 58542027, compound

Product 1

HCID 67225677HCID 67225677, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-[5-(2-amino-pyrimidin-5-yl)-1-tert-butyl-1H-benzimidazol-2-yl]-4-1,2,4-triazol-1-yl-phenol (100 mg, 0.23 mmol) in THF (3 mL) is added potassium carbonate (65 mg, 0.47 mmol) followed by isopropyl isocyanate (25 ul, 0.26 mmol). The resulting mixture is stirred at room temperature for 3 hours and then is warmed to 60° C. for 18 hours. The reaction is cooled to room temperature, poured into water and the product extracted into EtOAc (2×10 mL). The combined organics are dried with MgSO4 (500 mg), filtered, and concentrated. The remaining residue is purified by silica gel flash column chromatography (12 g silica gel, 0-5% MeOH/DCM). Product-containing fractions are combined and concentrated to give the title compound (15 mg, 13%). LCMS (ESMS): m/z 512.5 (M++1)

Workup

  1. temperatureis warmed to 60° C. for 18 hours
  2. temperatureThe reaction is cooled to room temperature
  3. extractionthe product extracted into EtOAc (2×10 mL)
  4. dry with materialThe combined organics are dried with MgSO4 (500 mg)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe remaining residue is purified by silica gel flash column chromatography (12 g silica gel, 0-5% MeOH/DCM)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-0e1f448d100c44458ae2d082b7232473
Source dataset
uspto-grants-2013_04
Patent number
US08420655B2

Reaction notes

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