Sodium Carbonate → HCID 62909416, compound

HRID 2205928Notes

Reaction equation

HRID 2205928 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:6][C:7]=1[Cl:8].Br[C:19]1[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=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:8][C:7]1[CH:6]=[CH:5][C:4]([C:19]2[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=2)=[CH:3][C:2]=1[NH2:1]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 1674331H-Pyrazole, 4-bromo-1-methyl-HCID 441187552-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

Product 1

HCID 62909416HCID 62909416, compoundYield 44.4%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
150 °C

Procedure

To a mixture of 3-amino-4-chlorophenylboronic acid pinacol ester (0.110 g, 0.434 mmol), 4-bromo-1-methylpyrazole (0.087 g, 0.54 mmol), 1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) DCM complex (24 mg, 0.029 mmol) was added anhydrous DME (2.5 mL) followed by 1M aqueous sodium carbonate (0.99 mL, 0.99 mmol). The microwave vial was heated at 150° C. for 20 minutes under microwave irradiation. Further catalyst (0.005 g) was added and the vial was heated at 130° C. for 10 minutes under microwave irradiation. The reaction mixture was partitioned between ethyl acetate (55 mL) and a saturated aqueous NaHCO3 solution (15 mL). The organic layer was washed with a saturated aqueous NaHCO3 solution (2×13 mL), dried (Na2SO4) and concentrated in vacuo. This residue was purified using preparative TLC eluting with 30% ethyl acetate in CH2Cl2. The product band was recovered and stirred with 2% MeOH in ethyl acetate/CH2Cl2 (v/v; 1:3) (20 mL). The silica was removed by filtration, washed with ethyl acetate/CH2Cl2 (v/v; 1:3) (2×5 mL) and acetone (3×4 mL) to give the title compound as an off-white solid (0.040 g, 44%). 1H-NMR (500 MHz, DMSO-d6) 3.84 (s, 3H), 5.29 (s, 2H), 6.72 (dd, J=2.1, 8.2 Hz, 1H), 6.94 (d, J=2.1 Hz, 1H), 7.14 (d, J=8.2 Hz, 1H), 7.68 (d, J=0.7 Hz, 1H), 7.98 (s, 1H).

Workup

  1. temperaturethe vial was heated at 130° C. for 10 minutes under microwave irradiation
  2. customThe reaction mixture was partitioned between ethyl acetate (55 mL)
  3. washThe organic layer was washed with a saturated aqueous NaHCO3 solution (2×13 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThis residue was purified
  7. washeluting with 30% ethyl acetate in CH2Cl2
  8. customThe product band was recovered
  9. customThe silica was removed by filtration
  10. washwashed with ethyl acetate/CH2Cl2 (v/v; 1:3) (2×5 mL) and acetone (3×4 mL)

Sources & evidence

ORD record
ord-5dc5746bcb054b5184812dfcd444013e
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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