9-Methyl-3,9-diazabicyclo[3.3.1]nonane--hydrogen chloride (1/2) → HCID 66639919, compound

HRID 1094531Notes

Reaction equation

HRID 1094531 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9]C(=O)C(F)(F)F)=[CH:5][C:4]=1[C:16]([F:19])([F:18])[F:17].Cl.Cl.[CH3:22][N:23]1[CH:28]2[CH2:29][CH2:30][CH2:31][CH:24]1[CH2:25][NH:26][CH2:27]2.C(N(C(C)C)C(C)C)C>CC#N>[CH3:22][N:23]1[CH:28]2[CH2:29][CH2:30][CH2:31][CH:24]1[CH2:25][N:26]([CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][C:4]=1[C:16]([F:17])([F:18])[F:19])[CH2:27]2

Participants

5

Reactant 3

HCID 189109-Methyl-3,9-diazabicyclo[3.3.1]nonane--hydrogen chloride (1/2)HCID 81531DiisopropylethylamineHCID 57351764N-[4-(Bromomethyl)-3-(trifluoromethyl)phenyl]-2,2,2-trifluoroacetamide

Product 1

HCID 66639919HCID 66639919, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of 296 mg (0.85 mMol) N-(4-bromomethyl-3-trifluoromethyl-phenyl)-2,2,2-trifluoro-acetamide (WO 2005/051366; Step 14.2) in 5 ml of CH3CN is added at 5° C. within 30 min to a solution of 213 mg (1.00 mMol) 9-methyl-3,9-diaza-bicyclo[3.3.1]nonane dihydrochloride (synthesized according to Barnes, Roderick A. et al.: J. Am. Chem. Soc. 1953, 75, 975) and 0.7 ml (4 mMol) ethyldiisopropylamine in 10 ml CH3CN. After 1.5 h at 5-10° C., the solvent is evaporated off under reduced pressure. The residue is dissolved in EtOAc and washed with NaHCO3. The aq. phase is re-extracted with EtOAc and the combined organics are washed with water, brine and dried over Na2SO4. The solvent is evaporated off under reduced pressure and the residue is dissolved in a mixture of 10 ml MeOH and 2 ml of a 2 M NaOH solution and stirred at 50° C. for 3 h. The MeOH is evaporated off under reduced pressure, the mixture is diluted with water and extracted 3 times with EtOAc. The combined organics are washed with water and brine and dried (Na2SO4). The solvent is evaporated off under reduced pressure to give the crude product which is purified by column chromatography (SiO2; CH2Cl2/EtOH/NH3 95:4.5:0.5) to afford the title compound as a crystalline solid.

Workup

  1. customthe solvent is evaporated off under reduced pressure
  2. dissolutionThe residue is dissolved in EtOAc
  3. washwashed with NaHCO3
  4. extractionThe aq. phase is re-extracted with EtOAc
  5. washthe combined organics are washed with water, brine
  6. dry with materialdried over Na2SO4
  7. customThe solvent is evaporated off under reduced pressure
  8. dissolutionthe residue is dissolved in a mixture of 10 ml MeOH and 2 ml of a 2 M NaOH solution
  9. customThe MeOH is evaporated off under reduced pressure
  10. additionthe mixture is diluted with water
  11. extractionextracted 3 times with EtOAc
  12. washThe combined organics are washed with water and brine
  13. dry with materialdried (Na2SO4)
  14. customThe solvent is evaporated off under reduced pressure
  15. customto give the crude product which
  16. customis purified by column chromatography (SiO2; CH2Cl2/EtOH/NH3 95:4.5:0.5)

Sources & evidence

ORD record
ord-137cea5a82b64ab485b1e6dbd662787b
Source dataset
uspto-grants-2012_03
Patent number
US08133886B2

Reaction notes

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