Water → HCID 58541956, compound

HRID 1966748Notes

Reaction equation

HRID 1966748 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+].I[CH2:40][CH3:41].O>CN(C=O)C.C(#N)C>[C:27]([N:12]1[C:11]2[CH:31]=[CH:32][C:8]([C:5]3[CH:4]=[N:3][C:2]([NH2:1])=[N:7][CH:6]=3)=[CH:9][C:10]=2[N:14]=[C:13]1[C:15]1[CH:16]=[C:17]([O:26][CH2:40][CH3:41])[CH:18]=[CH:19][C:20]=1[N:21]1[CH:25]=[N:24][CH:23]=[N:22]1)([CH3:29])([CH3:28])[CH3:30]

Participants

7

Reactant 4

HCID 962WaterHCID 6340IodoethaneHCID 11430Potassium CarbonateHCID 58542027HCID 58542027, compound

Product 1

HCID 58541956HCID 58541956, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

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 (50 mg, 0.12 mmol) in DMF (3 mL) is added potassium carbonate (24 mg, 0.18 mmol) followed by iodoethane (9.4 ul, 0.12 mmol). The resulting mixture is stirred at room temperature for 3 hours and then is warmed to 65° C. for 4 hours. The reaction is cooled to room temperature, poured into water and the product extracted into EtOAc (2×). The combined organics are dried (MgSO4), filtered, and concentrated. The remaining residue is purified by silica gel flash column chromatography (12 g silica gel, 2-8% MeOH/DCM). Product-containing fractions are combined and concentrated to give a solid which is diluted with acetonitrile. The white solid is collected via filtration and washed with acetonitrile to afford the title compound (20 mg, 38%). LCMS (ESMS): m/z 455.74 (M++1)

Workup

  1. temperatureis warmed to 65° C. for 4 hours
  2. temperatureThe reaction is cooled to room temperature
  3. extractionthe product extracted into EtOAc (2×)
  4. dry with materialThe combined organics are dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe remaining residue is purified by silica gel flash column chromatography (12 g silica gel, 2-8% MeOH/DCM)
  8. concentrationconcentrated
  9. customto give a solid which
  10. filtrationThe white solid is collected via filtration
  11. washwashed with acetonitrile

Sources & evidence

ORD record
ord-df6167a9c78b4de19e92e77ddf0f2e96
Source dataset
uspto-grants-2013_04
Patent number
US08420655B2

Reaction notes

Loading…