Cesium carbonate → HCID 67391011, compound

HRID 906450Notes

Reaction equation

HRID 906450 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[S:13]([N:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@@H:18]([CH2:29][OH:30])[CH2:17]1)(=[O:15])=[O:14].Br[CH2:32][C:33]([CH3:44])([CH3:43])[CH2:34][O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:22]([O:24][CH2:25][CH3:28])(=[O:23])[CH3:32].[CH3:11][CH2:2][CH2:3][CH:4]([CH3:9])[CH3:5].[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:32][C:33]([CH3:44])([CH3:43])[CH2:34][O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:37])[CH3:38])[CH:6]=[C:5]2[S:13]([N:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[C@@H:18]([CH2:29][OH:30])[CH2:17]1)(=[O:15])=[O:14]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 11780954(3-Bromo-2,2-dimethylpropoxy)(tert-butyl)dimethylsilaneHCID 67392085tert-Butyl (2R)-4-[(6-bromo-1-oxo-1,2-dihydroisoquinolin-4-yl)sulfonyl]-2-(hydroxymethyl)piperazine-1-carboxylate

Product 2

HCID 21882781Isohexane ethyl acetateYield 10%HCID 67391011HCID 67391011, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A solution of tert-butyl (2R)-4-[(6-bromo-1-oxo-1,2-dihydroisoquinolin-4-yl)sulfonyl]-2-(hydroxymethyl)piperazine-1-carboxylate (Example 49a, 0.855 g) dissolved in DMF (20 mL) was treated with (3-bromo-2,2-dimethylpropoxy)(tert-butyl)dimethylsilane (0.718 g) and cesium carbonate (1.109 g). The reaction was heated at 110° C. for 107 h. The reaction was cooled and partitioned between ethyl acetate and brine. The organics were washed with brine (×3), dried (MgSO4), filtered and evaporated to leave the crude product. This was purified (SiO2 chromatography, elution with 100% DCM then 10-50% ethyl acetate/isohexane) to afford the subtitle compound (0.580 g).

Workup

  1. temperatureThe reaction was cooled
  2. custompartitioned between ethyl acetate and brine
  3. washThe organics were washed with brine (×3)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customto leave the crude product
  8. customThis was purified (
  9. washSiO2 chromatography, elution with 100% DCM

Sources & evidence

ORD record
ord-c356dc1fed5747c5b78a0bd08fc5a88a
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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