Sodium Carbonate → HCID 68290941, compound

HRID 2205929Notes

Reaction equation

HRID 2205929 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][C:3]=1[Cl:17].Br[C:19]1[CH:24]=[N:23][CH:22]=[CH:21][N:20]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].COCCOC>[Cl:17][C:3]1[CH:4]=[C:5]([C:19]2[CH:24]=[N:23][CH:22]=[CH:21][N:20]=2)[CH:6]=[CH:7][C:2]=1[NH2:1]

Participants

6

Reactant 3

HCID 10340Sodium Carbonate2×HCID 6428002-Bromopyrazine2×HCID 441187962-Chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

Product 1

HCID 68290941HCID 68290941, compoundYield 44%

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
75 °C

Procedure

To a mixture of 4-amino-3-chlorophenylboronic acid pinacol ester (0.110 g, 0.434 mmol), 2-bromopyrazine (0.090 g, 0.56 mmol), 1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) DCM complex (24 mg, 0.029 mmol) was added anhydrous DME (3.0 mL) followed by 2M aqueous sodium carbonate (0.53 mL, 1.06 mmol). The microwave vial was heated at 75° C. for 40 minutes under microwave irradiation. Further catalyst (0.012 g) was added and the vial was heated at 90° C. for 25 minutes under microwave irradiation. Further 2-bromopyrazine (0.060 g), catalyst (12 mg) and 2M aqueous sodium carbonate (0.25 mL) were added and the reaction mixture was heated at 90° C. for an additional 30 minutes under microwave irradiation. The reaction was partitioned between ethyl acetate (60 mL) and a saturated aqueous NaHCO3 solution (15 mL). The organic layer was washed with a saturated aqueous NaHCO3 solution (2×15 mL), dried (Na2SO4) and concentrated in vacuo. The residue was purified using preparative TLC eluting with 7% ethyl acetate in CH2Cl2. The product band was recovered and stirred with 2% MeOH in ethyl acetate/CH2Cl2 (v/v; 1:10) (20 mL). The silica was removed by filtration, washed with ethyl acetate/CH2Cl2 (v/v; 1:5) (2×5 mL) and acetone (3×4 mL) to give the title compound as an off-white solid (0.039 g, 44%). 1H-NMR (500 MHz, DMSO-d6) 5.86 (s, 2H), 6.89 (d, J=8.5, 1H), 7.85 (dd, J=2.1, 8.5 Hz, 1H), 8.02 (d, J=2.1 Hz, 1H), 8.44 (d, J=2.5 Hz, 1H), 8.57 (dd, J=1.6, 2.5 Hz, 1H), 9.12 (d, J=1.5 Hz, 1H).

Workup

  1. temperaturethe vial was heated at 90° C. for 25 minutes under microwave irradiation
  2. temperaturethe reaction mixture was heated at 90° C. for an additional 30 minutes under microwave irradiation
  3. customThe reaction was partitioned between ethyl acetate (60 mL)
  4. washThe organic layer was washed with a saturated aqueous NaHCO3 solution (2×15 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified
  8. washeluting with 7% ethyl acetate in CH2Cl2
  9. customThe product band was recovered
  10. customThe silica was removed by filtration
  11. washwashed with ethyl acetate/CH2Cl2 (v/v; 1:5) (2×5 mL) and acetone (3×4 mL)

Sources & evidence

ORD record
ord-ecb8fa06981a4aac94ab0e53a448b3cf
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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