Cesium carbonate → 2-Bromo-6-(6-dimethylamino-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-4-fluoro-benzaldehyde

HRID 2245735Notes

Reaction equation

HRID 2245735 reaction equation
Br[C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([Br:11])[C:3]=1[CH:4]=[O:5].[CH3:12][N:13]([CH3:25])[C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[C:20](=[O:24])[NH:19][CH2:18][CH2:17]2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[Br:11][C:6]1[CH:7]=[C:8]([F:10])[CH:9]=[C:2]([N:19]2[CH2:18][CH2:17][C:16]3[C:21](=[CH:22][CH:23]=[C:14]([N:13]([CH3:12])[CH3:25])[CH:15]=3)[C:20]2=[O:24])[C:3]=1[CH:4]=[O:5]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 444746662,6-Dibromo-4-fluorobenzaldehydeHCID 574241216-(Dimethylamino)-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 592165352-Bromo-6-(6-dimethylamino-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-4-fluoro-benzaldehydeYield 48.9%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

Combined 0.948 g (3.4 mmol, 2 eq) 2,6-Dibromo-4-fluoro-benzaldehyde, 0.320 g (1.7 mmol, 1 eq) 6-Dimethylamino-3,4-dihydro-2H-isoquinolin-1-one, 29 mg Xantphos (0.050 mmol, 0.03 eq), 19 mg bis(dibenzylideneacetone)palladium (0.033 mmol, 0.02 eq), and 1.09 g Cesium Carbonate (3 mmol, 2.0 eq) in 5 ml dioxane, bubbled argon gas through the mixture for 1 minute, sealed the reaction vessel and heated at 100 C for 3 hours, then cooled to 80 C and heated for 14 hours. Cooled, diluted ethyl acetate, washed water 2×, brine, dried mgso4. Rotovaped, chromatographed (10% to 30% ea in hexanes) to give a solid, 325 mg 2-Bromo-6-(6-dimethylamino-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-4-fluoro-benzaldehyde. MS (ESI) 391.0 (M+H)+.

Workup

  1. customsealed the reaction vessel
  2. temperatureheated at 100 C for 3 hours
  3. temperaturecooled to 80 C
  4. temperatureheated for 14 hours
  5. temperatureCooled
  6. washdiluted ethyl acetate, washed water 2×, brine
  7. customdried mgso4
  8. customRotovaped, chromatographed (10% to 30% ea in hexanes)

Sources & evidence

ORD record
ord-aeda26ced446470abf9a412b0293e603
Source dataset
uspto-grants-2010_03
Patent number
US07683064B2

Reaction notes

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