5-Bromoisoquinoline → HCID 89499948, compound

HRID 1467812Notes

Reaction equation

HRID 1467812 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[CH3:12][N:13]([CH3:19])[C@H:14]1[CH2:18][CH2:17][NH:16][CH2:15]1.CC(C)([O-])C.[Na+]>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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH:7]1[C:8]2[C:3](=[C:2]([N:16]3[CH2:17][CH2:18][C@H:14]([N:13]([CH3:19])[CH3:12])[CH2:15]3)[CH:11]=[CH:10][CH:9]=2)[CH2:4][CH2:5][N:6]=1

Participants

6

Reactant 3

HCID 7364875-BromoisoquinolineHCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 23676156Sodium t-butoxide

Product 1

HCID 89499948HCID 89499948, compoundYield 82.3%

Reagents, catalysts & solvents 2

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
85 °C

Procedure

To 5-bromoisoquinoline (0.60 g, 2.88 mmol), (S)-N,N-dimethylpyrrolidin-3-amine (0.428 g, 3.75 mmol), Pd2(dba)3 (0.053 g, 0.058 mmol), BINAP (0.072 g, 0.115 mmol), and sodium tert-butoxide (0.39 g, 4.04 mmol) was added degassed toluene (10 mL) and the mixture was heated to 85° C. overnight. The reaction mixture was dissolved in EtOAc, washed with brine, dried over Na2SO4, filtered, and concentrated. This intermediate was reduced and then, oxidized as described in Example 1 to afford 206A (577 mg, 82%).

Workup

  1. customdegassed toluene (10 mL)
  2. dissolutionThe reaction mixture was dissolved in EtOAc
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-61e9a8fb2d294c428be60c823aa37c9a
Source dataset
uspto-grants-2015_04
Patent number
US09000172B2

Reaction notes

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