Dichloromethane → HCID 59402292, compound

HRID 2090454Notes

Reaction equation

HRID 2090454 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH:7]([CH3:19])[N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]2)=[CH:4][CH:3]=1.[CH3:20][N:21]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[N:22]1.C(=O)([O-])[O-].[K+].[K+].ClCCl>O1CCOCC1.O>[CH3:19][CH:7]1[CH2:6][C:5]2[C:10](=[CH:11][C:2]([C:24]3[CH:23]=[N:22][N:21]([CH3:20])[CH:25]=3)=[CH:3][CH:4]=2)[CH2:9][N:8]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 594022951,1-Dimethylethyl 7-bromo-3,4-dihydro-3-methyl-2(1H)-isoquinolinecarboxylate

Product 1

HCID 59402292HCID 59402292, compoundYield 97.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of tert-butyl 7-bromo-3-methyl-3,4-dihydroisoquinoline-2(1H)-carboxylate (0.326 g, 1.00 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.31 g, 1.50 mmol, Aldrich, Cat. No. 595314), in 1,4-dioxane (4.0 mL) was stirred at r.t. for 10 min. Potassium carbonate (415 mg, 3.00 mmol) in water (2.0 mL) was added to give a deep red solution. The mixture was degassed and refilled with nitrogen three times. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (35.0 mg, 0.0424 mmol) was added and the mixture was degassed and refilled with nitrogen three times and then heated at 120° C.)(oil bath temperature) for 3 h. After cooling, the mixture was diluted with ethyl acetate, washed with water and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with methanol in DCM (0-10%) to give the desired product (320 mg, 97.7%). LCMS (M+H)+: m/z=328.1.

Workup

  1. customto give a deep red solution
  2. customThe mixture was degassed
  3. additionrefilled with nitrogen three times
  4. customthe mixture was degassed
  5. additionrefilled with nitrogen three times
  6. temperatureAfter cooling
  7. additionthe mixture was diluted with ethyl acetate
  8. washwashed with water and brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by flash chromatography on a silica gel column with methanol in DCM (0-10%)

Sources & evidence

ORD record
ord-2af3e6e71c7d4b6a80f66a8dd44c1fe3
Source dataset
uspto-grants-2013_05
Patent number
US08436008B2

Reaction notes

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