6-Bromoisoquinoline → HCID 89601576, compound

HRID 530244Notes

Reaction equation

HRID 530244 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2.C([Li])CCC.[CH3:17][C:18]1([CH3:28])[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[C:20]([CH:26]=[O:27])=[CH:19]1>O1CCCC1>[CH:8]1[C:9]2[C:4](=[CH:3][C:2]([CH:26]([C:20]3[C:21]([CH3:25])([CH3:24])[CH2:22][CH2:23][C:18]([CH3:28])([CH3:17])[CH:19]=3)[OH:27])=[CH:11][CH:10]=2)[CH:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 3136816-BromoisoquinolineHCID 89600966HCID 89600966, compoundHCID 178418339Butyllithium

Product 1

HCID 89601576HCID 89601576, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 6-bromoisoquinoline (416 mg, 2 mmol) in tetrahydrofuran (8 mL) was added dropwise into n-butyl lithium (1.6 M in hexane, 1.25 mL, 2 mmol) at −78° C. and the reaction was stirred for 30 minutes. A solution of the product of Example 10g (150 mg, 1 mmol) in tetrahydrofuran (2 mL) was added and the reaction was stirred at −78° C. for 1 hour and then slowly warmed to room temperature. The mixture was quenched with the addition of saturated aqueous ammonium chloride and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated aqueous sodium bicarbonate, brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to afford the title compound (167.3 mg, Yield: 63%). 1H NMR (400 MHz, CDCl3) δ 9.22 (s, 1H), 8.52 (d, J=6.0 Hz, 2H), 7.96 (d, J=8.8 Hz, 2H), 7.49 (d, J=8.4 Hz, 1H), 5.49 (s, 1H), 5.32 (d, J=15.2 Hz, 1H), 1.63-1.44 (m, 4H), 1.21 (s, 3H), 1.01 (s, 3H), 0.97 (s, 3H), 0.91 (s, 3H) ppm.

Workup

  1. stirringthe reaction was stirred at −78° C. for 1 hour
  2. customThe mixture was quenched with the addition of saturated aqueous ammonium chloride
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic phase was washed with saturated aqueous sodium bicarbonate, brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f236aeb4ad6f43d994fd3e24ff1b0722
Source dataset
uspto-grants-2016_05
Patent number
US09353063B2

Reaction notes

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