Cesium carbonate → HCID 86671317, compound

HRID 1472925Notes

Reaction equation

HRID 1472925 reaction equation
Br[C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1.[C:10]([C:12]1[CH:13]=[C:14](B(O)O)[CH:15]=[CH:16][C:17]=1[F:18])#[N:11].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[F:18][C:17]1[CH:16]=[CH:15][C:14]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]([CH:8]=[O:9])[N:7]=2)=[CH:13][C:12]=1[C:10]#[N:11]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27570096-Bromopyridine-2-carbaldehydeHCID 27579643-Cyano-4-fluorophenylboronic acid

Product 1

HCID 86671317HCID 86671317, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 6-bromopicolinaldehyde (1.00 g, 5.38 mmol) in dioxane (30 mL) at ambient temperature was added 3-cyano-4-fluorophenylboronic acid (0.887 g, 5.38 mmol), 2M cesium carbonate (8.1 mL, 16.2 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.220 g, 0.269 mmol). The mixture was degassed (3× vacuum/purge N2), then heated at 80° C. overnight. The mixture was cooled, concentrated and partitioned between water and CH2Cl2. The organic layer was concentrated and purified by chromatography (30% ethyl acetate:hexanes) to provide 2-fluoro-5-(6-formylpyridin-2-yl)benzonitrile. To a solution of 2-fluoro-5-(6-formylpyridin-2-yl)benzonitrile (0.500 g, 2.21 mmol) in methanol (20 mL) at ambient temperature was added D-valinol (0.25 mL, 2.2 mmol), acetic acid (0.50 mL, 8.8 mmol) followed by MP-cyanoborohydride (2.49 mmol/g; 1.0 g). After 2 hours, the mixture was filtered, concentrated, and the residue partitioned between ether and 1M NaOH. The organic layer was concentrated and purified by chromatography to provide 362 mg (52%) of the title compound. MS (DCI+) m/z 314 (M+H); 1H NMR (400 MHz, DMSO-d6) δ 8.62 (dd, J=6.3, 2.3 Hz, 1H), 8.52 (ddd, J=8.9, 5.3, 2.4 Hz, 1H), 7.97-7.84 (m, 2H), 7.66 (t, J=9.0 Hz, 1H), 7.49 (dd, J=7.4, 1.1 Hz, 1H), 3.92 (d, J=3.6 Hz, 2H), 3.52-3.43 (m, 1H), 2.40-2.22 (m, 2H), 1.93-1.76 (m, 1H), 0.89 (dd, J=9.5, 6.9 Hz, 6H).

Workup

  1. customThe mixture was degassed
  2. custom(3× vacuum/purge N2)
  3. temperatureThe mixture was cooled
  4. concentrationconcentrated
  5. custompartitioned between water and CH2Cl2
  6. concentrationThe organic layer was concentrated
  7. custompurified by chromatography (30% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-37da5bdb838543b88014cf169baec5ac
Source dataset
uspto-grants-2015_04
Patent number
US09012651B2

Reaction notes

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