Potassium Carbonate → 2-chloro-5-(4-chloro-6-quinolinyl)-N,N-dimethyl-3-pyridinamine

HRID 1963788Notes

Reaction equation

HRID 1963788 reaction equation
[Cl:1][C:2]1[C:7]([N:8]([CH3:10])[CH3:9])=[CH:6][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][N:3]=1.Br[C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[N:27]=[CH:26][CH:25]=[C:24]2[Cl:31].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1>[Cl:1][C:2]1[C:7]([N:8]([CH3:9])[CH3:10])=[CH:6][C:5]([C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[N:27]=[CH:26][CH:25]=[C:24]3[Cl:31])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 51395376-Bromo-4-chloroquinolineHCID 582294462-chloro-N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine

Product 1

HCID 446101612-chloro-5-(4-chloro-6-quinolinyl)-N,N-dimethyl-3-pyridinamineYield 71.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

(Some starting materials may be obtained from ECA International, Palatine, Ill.) To a microwave vial (5 mL), 2-chloro-N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine (0.110 g, 0.390 mmol), 6-bromo-4-chloroquinoline (0.102 g, 0.419 mmol), PdCl2 (dppf)-CH2Cl2 adduct (0.0183 g, 0.0224 mmol) and potassium carbonate (0.500 mL, 1.00 mmol) were added into 1,4-dioxane (3 mL). The mixture was degassed by bubbling nitrogen through for 10 min. The tube was irradiated with microwave at 100° C. for 10 min. The reaction was cooled to RT then partitioned between water (20 mL) and EtOAc (20 mL). The aqueous phase was extracted with EtOAc (2×20 mL). The combined organic phases were washed with saturated aqueous NaCl (40 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (eluent: acetone in hexanes 0% -30%) to afford the title compound as a white solid (0.0884 g). m/z: calc'd for C16H13Cl2N3; 317.0, found: 318.1 (M+1). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.97 (s, 6 H), 7.55-7.63 (m, 2 H), 7.98 (dd, J=8.8, 2.0 Hz, 1 H), 8.25 (d, J=8.8 Hz, 1 H), 8.38 (dd, J=5.3, 2.0 Hz, 2 H), 8.84 (d, J=4.7 Hz, 1 H).

Workup

  1. customThe mixture was degassed
  2. customby bubbling nitrogen through for 10 min
  3. customThe tube was irradiated with microwave at 100° C. for 10 min
  4. customthen partitioned between water (20 mL) and EtOAc (20 mL)
  5. extractionThe aqueous phase was extracted with EtOAc (2×20 mL)
  6. washThe combined organic phases were washed with saturated aqueous NaCl (40 mL)
  7. dry with materialThe organic phase was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by column chromatography (eluent: acetone in hexanes 0% -30%)

Sources & evidence

ORD record
ord-5012a0c202e94f5aa07e558e46c99e36
Source dataset
uspto-grants-2013_04
Patent number
US08415376B2

Reaction notes

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