Cesium carbonate → HCID 10112406, compound

HRID 1745904Notes

Reaction equation

HRID 1745904 reaction equation
C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[CH:16][CH:17]=[C:18]3[C:23]=2[N:22]=[C:21]([N:24]2[C:28]4[CH:29]=[CH:30][C:31]([OH:33])=[CH:32][C:27]=4[N:26]=[CH:25]2)[CH:20]=[CH:19]3)[CH2:10][CH2:9]1)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+].[Br-].[CH:42]1([CH3:45])[CH2:44][CH2:43]1>CN(C=O)C.C(O)(C(F)(F)F)=O>[CH:42]1([CH2:45][O:33][C:31]2[CH:30]=[CH:29][C:28]3[N:24]([C:21]4[CH:20]=[CH:19][C:18]5[C:23](=[C:14]([N:11]6[CH2:12][CH2:13][CH:8]([NH2:7])[CH2:9][CH2:10]6)[CH:15]=[CH:16][CH:17]=5)[N:22]=4)[CH:25]=[N:26][C:27]=3[CH:32]=2)[CH2:44][CH2:43]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 22042231HCID 22042231, compoundHCID 68809961HCID 68809961, compound

Product 1

HCID 10112406HCID 10112406, compoundYield 65.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
65 °C

Procedure

{1-[2-(5-Hydroxy-benzoimidazol-1-yl)-quinolin-8-yl]-piperidin-4-yl}-carbamic acid tert-butyl ester 3A (200 mg, 0.435 mMol) was dissolved in 1.5 mL of anhydrous DMF under an atmosphere of dry N2. To this solution was added Cs2CO3 (170 mg, 0.520 mMol) followed by cyclopropyl methane bromide (46 μL, 0.48 mMol). The reaction mixture was subsequently heated to 65° C. and stirred at this temperature for 4 hours. The reaction mixture was then cooled to ambient temperature and partitioned between EtOAc and water. The EtOAc layer was washed 4 more times with water and then with brine. The EtOAc was then dried over Na2SO4, filtered and concentrated under vacuum and the resulting green oil was chromatographed on flash silica gel eluting with MeOH/DCM (2:98) to give the a green oil. The oil was dissolved in 1.5 mL of TFA under an atmosphere of dry N2. The reaction mixture was stirred at ambient temperature for 10 minutes after which time it was concentrated under vacuum and the resulting residue was partitioned between DCM and aqueous 0.1 N NaOH. The DCM layer was then washed with basic brine (pH 10), dried over Na2SO4, filtered and concentrated under vacuum to give 118 mg of the title compound as a yellow solid 32.

Workup

  1. temperatureThe reaction mixture was then cooled to ambient temperature
  2. custompartitioned between EtOAc and water
  3. washThe EtOAc layer was washed 4 more times with water
  4. dry with materialThe EtOAc was then dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customthe resulting green oil was chromatographed on flash silica gel eluting with MeOH/DCM (2:98)
  8. customto give the a green oil
  9. stirringThe reaction mixture was stirred at ambient temperature for 10 minutes after which time it
  10. concentrationwas concentrated under vacuum
  11. customthe resulting residue was partitioned between DCM and aqueous 0.1 N NaOH
  12. washThe DCM layer was then washed with basic brine (pH 10)
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-702738e07ed448f99c5ae87322c50e41
Source dataset
uspto-grants-2006_03
Patent number
US07019147B1

Reaction notes

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