2,6-Lutidine → HCID 86721354, compound

HRID 869525Notes

Reaction equation

HRID 869525 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:33]=1)[O:7][CH2:8][C:9]1[CH:19]=[C:18]([CH2:20][N:21]3[C:25]4[CH:26]=[CH:27][CH:28]=[C:29]([OH:30])[C:24]=4[N:23]=[C:22]3[CH2:31][OH:32])[CH:17]=[CH:16][C:10]=1/[C:11]/2=[C:12](/[CH3:15])\[C:13]#[N:14].N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si:48]([C:51]([CH3:54])([CH3:53])[CH3:52])([CH3:50])[CH3:49])(=O)=O.C(=O)([O-])O.[Na+].C(=O)([O-])[O-].[K+].[K+]>ClCCl.O>[O:32]([CH2:31][C:22]1[N:21]([CH2:20][C:18]2[CH:17]=[CH:16][C:10]3/[C:11](=[C:12](/[CH3:15])\[C:13]#[N:14])/[C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:33][C:6]=4[O:7][CH2:8][C:9]=3[CH:19]=2)[C:25]2[CH:26]=[CH:27][CH:28]=[C:29]([OH:30])[C:24]=2[N:23]=1)[Si:48]([C:51]([CH3:54])([CH3:53])[CH3:52])([CH3:50])[CH3:49]

Participants

8

Reactant 5

HCID 79372,6-LutidineHCID 11430Potassium CarbonateHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 516892Sodium BicarbonateHCID 86721349HCID 86721349, compound

Product 1

HCID 86721354HCID 86721354, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

[step 1] (E)-2-(3-fluoro-8-{[4-hydroxy-2-(hydroxymethyl)-1H-benzo[d]imidazol-1-yl]methyl}dibenzo[b,e]oxepin-11(6H)-ylidene)propanenitrile (245 mg, 0.56 mmol) obtained in Reference Example 2A, step 4 was dissolved in dichloromethane (2.8 mL), 2,6-lutidine (0.22 mL, 1.89 mmol) and tert-butyldimethylsilyl trifluoromethanesulfonate (0.38 mL, 1.67 mmol) were added under ice-cooling, and the mixture was stirred at room temperature for 1 hr. To the mixture was added saturated aqueous sodium hydrogen carbonate, and the mixture was extracted 3 times with chloroform. The combined organic layers were washed with 1 mol/L hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was dissolved in methanol (2.8 mL), potassium carbonate (384 mg, 2.77 mmol) was added, and the mixture was stirred at room temperature for 13 hr. Water was added to the mixture, and the mixture was extracted 3 times with chloroform. The combined organic layers were dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=100/0 v/v-85/15 v/v) to give (E)-2-[8-({2-[(tert-butyldimethylsiloxy)methyl]-4-hydroxy-1H-benzo[d]imidazol-1-yl}methyl)-3-fluorodibenzo[b,e]oxepin-11(6H)-ylidene]propanenitrile (203 mg, 66%).

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted 3 times with chloroform
  3. washThe combined organic layers were washed with 1 mol/L hydrochloric acid and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe obtained residue was dissolved in methanol (2.8 mL)
  7. stirringthe mixture was stirred at room temperature for 13 hr
  8. extractionthe mixture was extracted 3 times with chloroform
  9. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (chloroform/methanol=100/0 v/v-85/15 v/v)

Sources & evidence

ORD record
ord-0942aec2e697469bba0590453cae57d6
Source dataset
uspto-grants-2015_03
Patent number
US08969345B2

Reaction notes

Loading…