Cesium carbonate → tert-Butyl 4-[(6-bromo-2-{[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclobutyl]methyl}-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]piperazine-1-carboxylate

HRID 906427Notes

Reaction equation

HRID 906427 reaction equation
[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[CH2:13][N:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:38][C:39]1([CH2:43][O:44][Si:45]([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46])[CH2:42][CH2:41][CH2:40]1)(=O)=O>CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:38][C:39]1([CH2:43][O:44][Si:45]([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46])[CH2:42][CH2:41][CH2:40]1)[CH:6]=[C:5]2[CH2:13][N:14]1[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:18][CH2:19]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 67390749tert-Butyl 4-[(6-bromo-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]piperazine-1-carboxylateHCID 86640970[1-({[Tert-butyl(dimethyl)silyl]oxy}methyl)cyclobutyl]methyl methanesulfonate

Product 1

HCID 67390960tert-Butyl 4-[(6-bromo-2-{[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclobutyl]methyl}-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]piperazine-1-carboxylateYield 59.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of tert-butyl 4-[(6-bromo-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]piperazine-1-carboxylate (Example 27b, 0.171 g) dissolved in DMF (5 mL) was treated with cesium carbonate (0.264 g) and [1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclobutyl]methyl methanesulfonate [Archiv der Pharmazie (Weinheim, Germany), 2005, 338 (11), 522-7] (0.187 g) under nitrogen. The resulting mixture was stirred at 70° C. for 7 h. The reaction was diluted with water (300 mL), and extracted with diethyl ether (300 mL×3). The organic was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified (SiO2 chromatography, elution with 6-12% ethyl acetate/isohexane) to afford the subtitle compound (0.153 g).

Workup

  1. extractionextracted with diethyl ether (300 mL×3)
  2. dry with materialThe organic was dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified
  7. wash(SiO2 chromatography, elution with 6-12% ethyl acetate/isohexane)

Sources & evidence

ORD record
ord-48ff335990b54692abd971445d8e73fe
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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