Dimethylacetamide → HCID 89649303, compound

HRID 1773945Notes

Reaction equation

HRID 1773945 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[C:14]([Cl:22])[CH:15]=[CH:16][C:17]=2Br)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[C:24]([N:26](C)C)=O>CCOC(C)=O.O.[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].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]>[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[C:14]([Cl:22])[CH:15]=[CH:16][C:17]=2[C:24]#[N:26])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 2

HCID 31374DimethylacetamideHCID 89649186HCID 89649186, compound

Product 1

HCID 89649303HCID 89649303, compound

Reagents, catalysts & solvents 5

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst2×HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst2×HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalyst2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 5-bromo-8-chloro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (381 mg, 1.00 mmol, 1.00 eq.) in DMAC (2 mL), zinc cyanide (59 mg, 0.50 mmol, 0.50 eq.), tris(dibenzylideneacetone)dipalladium(O) (20 mg, 0.02 mmol, 0.02 eq.), 1,1′-bis-(diphenylphosphino)-ferrocene (15 mg, 0.03 mmol, 0.03 eq.) and poly(methylhydrosiloxane) (20 μL) were added. The resulting mixture was stirred at 150° C. under microwave irradiation for 30 min. The mixture was allowed to cool to r.t. To the previous mixture, zinc cyanide (59 mg, 0.50 mmol, 0.50 eq.), tris(dibenzylideneacetone)dipalladium(O) (20 mg, 0.02 mmol, 0.02 eq.), 1,1′-bis-(diphenylphosphino)-ferrocene (15 mg, 0.03 mmol, 0.03 eq.) and poly(methylhydrosiloxane) (20 μL) were added. The resulting mixture was stirred at 150° C. under microwave irradiation for 30 min. The reaction mixture was diluted with AcOEt and water was added. The layers were separated and the org. layer was dried over MgSO4, filtered over celite, and concentrated in vacuo. The residue was purified by flashmaster (column: 25 g, flow: 30 mL/min, 40 fractions of 30 mL, Heptane+5% AcOEt to Heptane+30% AcOEt) to yield the title compound as a yellow oil.

Workup

  1. temperatureto cool to r.t
  2. stirringThe resulting mixture was stirred at 150° C. under microwave irradiation for 30 min
  3. additionwas added
  4. customThe layers were separated
  5. dry with materiallayer was dried over MgSO4
  6. filtrationfiltered over celite
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flashmaster (column: 25 g, flow: 30 mL/min, 40 fractions of 30 mL, Heptane+5% AcOEt to Heptane+30% AcOEt)

Sources & evidence

ORD record
ord-636d5c31789a454a924a6725fb405252
Source dataset
uspto-grants-2016_02
Patent number
US09255090B2

Reaction notes

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