Chlorosuccinimide → 8-amino-5-chloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one

HRID 577489Notes

Reaction equation

HRID 577489 reaction equation
[Cl:1]N1C(=O)CCC1=O.[NH2:9][C:10]1[C:11]([O:21][CH3:22])=[CH:12][CH:13]=[C:14]2[C:19]=1[C:18](=[O:20])[NH:17][CH2:16][CH2:15]2>CN(C)C=O>[NH2:9][C:10]1[C:11]([O:21][CH3:22])=[CH:12][C:13]([Cl:1])=[C:14]2[C:19]=1[C:18](=[O:20])[NH:17][CH2:16][CH2:15]2

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 867237148-amino-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 867237158-amino-5-chloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-oneYield 44.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-chlorosuccinimide (20 g, 0.147 mol) was added to a solution of 8-amino-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (296c, 24 g, 0.125 mol) in N,N-dimethylformamide (250 mL) and stirred at room temperature overnight. The solution was partitioned between water (100 mL) and ethyl acetate (5×100 mL). The combined organic extracts were washed with brine (5×100 mL), dried over sodium sulfate, and concentrated to dryness. The residue was triturated with acetonitrile (200 mL), and the solids collected by filtration. After drying, 8-amino-5-chloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (296d, 12.5 g, 44% yield) was obtained as a blue solid. 1H NMR (400 MHz, DMSO-d6): δ 7.84 (s, 1H), 6.93 (s, 1H), 3.80 (s, 3H), 3.29-3.25 (m, 2H), 2.81-2.78 (t, J=6.6 Hz, 2H).

Workup

  1. customThe solution was partitioned between water (100 mL) and ethyl acetate (5×100 mL)
  2. washThe combined organic extracts were washed with brine (5×100 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated to dryness
  5. customThe residue was triturated with acetonitrile (200 mL)
  6. filtrationthe solids collected by filtration
  7. customAfter drying

Sources & evidence

ORD record
ord-c57dce3c02c245e290d7ee651e097e8a
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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