HCID 65470943, compound → HCID 24957483, compound

HRID 336637Notes

Reaction equation

HRID 336637 reaction equation
C([Li])CCC.[CH3:6][O:7][C:8]1[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[C:13]([CH3:19])[C:9]=1[C:10]([NH2:12])=[O:11].[CH3:20][N:21]([CH3:35])[CH2:22][CH2:23][O:24][C:25]1[C:32]([CH3:33])=[CH:31][C:28]([C:29]#N)=[CH:27][C:26]=1[CH3:34]>C1COCC1>[CH3:20][N:21]([CH3:35])[CH2:22][CH2:23][O:24][C:25]1[C:32]([CH3:33])=[CH:31][C:28]([C:29]2[NH:12][C:10](=[O:11])[C:9]3[C:13]([CH:19]=2)=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:8]=3[O:7][CH3:6])=[CH:27][C:26]=1[CH3:34]

Participants

5

Reactant 3

HCID 65470943HCID 65470943, compoundHCID 66661473HCID 66661473, compoundHCID 178418339Butyllithium

Product 1

HCID 24957483HCID 24957483, compoundYield 8.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

n-Butyl lithium (4.2 mL, 10.54 mmol, 2.5 M solution in hexane) was added slowly to a solution of 2,4-dimethoxy-6-methyl benzamide (958 mg, 4.58 mmol) in THF (30 mL) under nitrogen with cooling (ice-salt bath), maintaining the temperature below 20° C. After completion of the addition, the mixture was stirred for 1 h at 0° C., then cooled to −50° C. and a solution of 4-(2-dimethylamino ethoxy)-3,5-dimethyl benzonitrile (1.1 g, 5.04 mmol) (the B-ring building block) in THF (10 mL) was added quickly. The cooling bath was removed and the reaction mixture was allowed to warm to room temperature and stirred for 16 h at room temperature. A saturated NH4Cl solution was added with cooling and the layers' were separated. The organic layer was washed with water, brine, dried over Na2SO4 and concentrated to give crude product. The crude product was purified by chromatography to give 3-(4-(2-(dimethylamino)ethoxy)-3,5-dimethylphenyl)-6,8-dimethoxyisoquinolin-1(2H)-one (162 mg, 8%) as a hydrochloride. Selected data: MS (ES) m/z: 397.06; MP 261-263° C. at decomposition (HCl).

Workup

  1. temperaturemaintaining the temperature below 20° C
  2. additionAfter completion of the addition
  3. temperaturecooled to −50° C.
  4. customThe cooling bath was removed
  5. temperatureto warm to room temperature
  6. stirringstirred for 16 h at room temperature
  7. additionA saturated NH4Cl solution was added
  8. temperaturewith cooling
  9. customthe layers' were separated
  10. washThe organic layer was washed with water, brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated
  13. customto give crude product
  14. customThe crude product was purified by chromatography

Sources & evidence

ORD record
ord-d69330af9bbb46a7a1b86bd33e35f9b8
Source dataset
uspto-grants-2014_11
Patent number
US08889698B2

Reaction notes

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