Cesium carbonate → HCID 57419170, compound

HRID 2390410Notes

Reaction equation

HRID 2390410 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH:15]=[C:14]([CH2:19][CH2:20]OS(C)(=O)=O)[CH:13]=[CH:12]3)[CH:6]=[N:7][CH:8]=1)#[N:2].[CH3:26][C@@H:27]1[CH2:31][CH2:30][CH2:29][NH:28]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[CH3:26][C@@H:27]1[CH2:31][CH2:30][CH2:29][N:28]1[CH2:20][CH2:19][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[CH:10]=[C:9]([C:5]1[CH:6]=[N:7][CH:8]=[C:3]([CH:4]=1)[C:1]#[N:2])[CH:18]=[CH:17]2

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 641544(R)-2-MethylpyrrolidineHCID 86593848HCID 86593848, compound

Product 1

HCID 57419170HCID 57419170, compoundYield 57.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Methanesulfonic acid 2-[6-(5-cyano-pyridin-3-yl)-naphthalen-2-yl]-ethyl ester (Example 81B, 190 mg, 0.54 mmol), (2R)-2-methylpyrrolidine (138 mg, 1.62 mmol, 3.0 equiv.), and cesium carbonate (176 mg, 0.54 mmol) in anhydrous acetonitrile (6 mL) were stirred in a sealed tube at 50° C. for 18 hours. The reaction mixture was concentrated under reduced pressure. The residue was partitioned between ethyl acetate and saturated aqueous Na2CO3. The organic layer was washed with brine, then dried (MgSO4), and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (98:2:trace dichloromethane/methanol/NH4OH). Fractions containing product were combined and concentrated under reduced pressure to provide the free base of the title compound as a white solid (105.9 mg, 57% yield). This free base was dissolved in methanol and treated with excess dioxane-HCl. Ether was added to induce crystallization of the dihydrochloride salt of the title compound. 1H NMR (CD3OD, 300 MHz) δ 9.26 (br s, 1H), 8.97 (br s, 1H), 8.68 (s, 1H), 8.29 (s, 1H), 8.05 (s, 1H), 8.02 (s, 1H), 7.90 (br s, 1H), 7.88 (dd, J=2, 9 Hz, 1H), 7.56 (d, J=8 Hz, 1H), 3.84-3.49 (m, 7H), 2.45-2.30 (m, 1H), 2.27-1.99 (m, 2H), 1.84-1.69 (m, 1H), 1.50 (d, J=6 Hz, 3H). MS (DCI-NH3) [M+H]+ at 342.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customThe residue was partitioned between ethyl acetate and saturated aqueous Na2CO3
  3. washThe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by column chromatography (98:2:trace dichloromethane/methanol/NH4OH)
  8. additionFractions containing product
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ebf0b961df18437cb8347f29b436f652
Source dataset
uspto-grants-2012_09
Patent number
US08273767B2

Reaction notes

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