Sodium Hydroxide → tert-Butyl (3R)-4-[(6-bromo-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]-3-methylpiperazine-1-carboxylate

HRID 906433Notes

Reaction equation

HRID 906433 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7](S(C1C=CC=CC=1)(=O)=O)[CH:6]=[C:5]2[CH2:22]Br.[CH3:24][C@H:25]1[NH:30][CH2:29][CH2:28][N:27]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:26]1.C(N(CC)C(C)C)(C)C.[OH-].[Na+]>C1COCC1.CO.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][CH:6]=[C:5]2[CH2:22][N:30]1[CH2:29][CH2:28][N:27]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:26][C@H:25]1[CH3:24]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 2756811(R)-1-Boc-3-methylpiperazineHCID 671303306-Bromo-4-(bromomethyl)-2-(phenylsulfonyl)isoquinolin-1(2H)-one

Product 1

HCID 86640971tert-Butyl (3R)-4-[(6-bromo-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]-3-methylpiperazine-1-carboxylateYield 39.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

6-Bromo-4-(bromomethyl)-2-(phenylsulfonyl)isoquinolin-1(2H)-one (Example 11d, 2.0 g), tert-butyl (3R)-3-methylpiperazine-1-carboxylate (0.946 g) and N,N-diisopropylethylamine (1.143 mL) were dissolved in THF (10 mL) and stirred at room temperature under nitrogen for 16 h. The reaction mixture was diluted with methanol (10 mL) and treated with sodium hydroxide (0.35 g), after stirring at room temperature for 1 h, water (200 mL) was added and the reaction mixture extracted into ethyl acetate (250 mL). The separated organic layer was dried (MgSO4) filtered and evaporated, the residue was purified (SiO2 chromatography, elution with ethyl acetate) to give the subtitle compound (0.75 g) as a solid.

Workup

  1. stirringafter stirring at room temperature for 1 h
  2. extractionthe reaction mixture extracted into ethyl acetate (250 mL)
  3. dry with materialThe separated organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customthe residue was purified
  7. wash(SiO2 chromatography, elution with ethyl acetate)

Sources & evidence

ORD record
ord-0b26a99282e44528ae171be57676269d
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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