Sodium Carbonate → 4-(5-Phenyl-pyridin-3-yl)-1,4-diaza-bicyclo[3.2.1]octane dihydrochloride

HRID 2117259Notes

Reaction equation

HRID 2117259 reaction equation
[ClH:1].Cl.Br[C:4]1[CH:5]=[C:6]([N:10]2[CH:16]3[CH2:17][N:13]([CH2:14][CH2:15]3)[CH2:12][CH2:11]2)[CH:7]=[N:8][CH:9]=1.[C:18]1(B(O)O)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+]>CCO.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[ClH:1].[ClH:1].[C:18]1([C:4]2[CH:5]=[C:6]([N:10]3[CH:16]4[CH2:17][N:13]([CH2:14][CH2:15]4)[CH2:12][CH2:11]3)[CH:7]=[N:8][CH:9]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 693144864-(5-Bromo-pyridin-3-yl)-1,4-diaza-bicyclo[3.2.1]octane dihydrochoride

Product 1

HCID 100427354-(5-Phenyl-pyridin-3-yl)-1,4-diaza-bicyclo[3.2.1]octane dihydrochlorideYield 157.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×

Procedure

4-(5-Bromo-pyridin-3-yl)-1,4-diaza-bicyclo[3.2.1]octane dihydrochoride (50 mg, 0.15 mmol) was added to a mixture of phenylboronic acid (25 mg, 0.20 mmol), tetrakis(triphenylphosphine)palladium(0) (7 mg, 0.006 mmol), sodium carbonate (63 mg, 0.60 mmol) in EtOH (5 mL) and water (5 mL). The reaction mixture was placed in an oil bath at 80° C. for 3 h, and then 60° C. for 18 h. The mixture was cooled to RT, diluted with water (10 mL) and extracted with EtOAc (3×15 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The residue was dissolved in EtOH (10 mL) and conc. HCl (0.2 mL) was added. The mixture was concentrated and EtOH (10 mL) was added and the solution was concentrated. This procedure was repeated three times and the resulting solid was triturated in EtOAc. The remaining solids were collected via filtration to give 40 mg (78%) of the title compound: (data for free base) 1H NMR (CD3OD, 400 MHz) δ 8.55 (br s, 1H), 8.50 (br s, 1H), 8.33 (br s, 1H), 7.83-7.81 (m, 2H), 7.60-7.53 (m, 3H), 5.12 (br s, 1H), 4.06-4.04 (m, 1H), 3.70-3.59 (m, 5H), 3.54-3.51 (m, 2H), 2.51-2.47 (m, 1H), 2.26-2.23 (m, 1H); APCI MS m/z 266.2 (M+1).

Workup

  1. wait60° C. for 18 h
  2. extractionextracted with EtOAc (3×15 mL)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in EtOH (10 mL)
  7. additionconc. HCl (0.2 mL) was added
  8. concentrationThe mixture was concentrated
  9. additionEtOH (10 mL) was added
  10. concentrationthe solution was concentrated
  11. customthe resulting solid was triturated in EtOAc
  12. filtrationThe remaining solids were collected via filtration

Sources & evidence

ORD record
ord-317c1b119f464b2fb0bda723b9be570a
Source dataset
uspto-grants-2008_10
Patent number
US07442694B2

Reaction notes

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