Dichloromethane → HCID 86732562, compound

HRID 711414Notes

Reaction equation

HRID 711414 reaction equation
[C:1]([O:5][C:6](=[O:32])[NH:7][CH2:8][CH2:9][CH:10]1[N:15]2[C:16](I)=[C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([O:25][C:26]([F:29])([F:28])[F:27])[CH:20]=3)[CH:18]=[C:14]2[C:13](=[O:31])[NH:12][CH2:11]1)([CH3:4])([CH3:3])[CH3:2].[S:33]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34]1.ClCCl.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O>[C:1]([O:5][C:6](=[O:32])[NH:7][CH2:8][CH2:9][CH:10]1[N:15]2[C:16]([C:35]3[CH:36]=[CH:37][S:33][CH:34]=3)=[C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([O:25][C:26]([F:29])([F:28])[F:27])[CH:20]=3)[CH:18]=[C:14]2[C:13](=[O:31])[NH:12][CH2:11]1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 581760Thiophene-3-boronic acidHCID 86732561HCID 86732561, compound

Product 1

HCID 86732562HCID 86732562, compoundYield 54.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of tert-butyl(2-{6-iodo-1-oxo-7-[3-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl}ethyl)carbamate (100 mg, 0.177 mmol) in 3 ml of 1,4-dioxane and 1 ml of water, under argon atmosphere, (67.9 mg, 0.531 mmol) of 3-thienylboronic acid, 7.2 mg (0.009 mmol) of 1,1′-bis(diphenylphosphino)ferrocenepalladium, complex with dichloromethane and 172 mg (0.531 mmol) of cesium carbonate, were subsequently added. The mixture was heated at 80° for 1 hour in a sealed vial. The reaction was filtered through a celite pad and the solvent evaporated to dryness. The crude was then portioned between ethyl acetate and water, the organic layer dried over sodium sulphate and the solvent removed in vacuo. After purification by flash chromatography on silica gel column (DCM/EtOAc/EtOH 6/4/0.5), and further purification by HPLC/MS preparative method 1, 50 mg (54%) of tert-butyl(2-{1-oxo-6-(thiophen-3-yl)-7-[3-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl}ethyl)carbamate were obtained.

Workup

  1. temperatureThe mixture was heated at 80° for 1 hour in a sealed vial
  2. filtrationThe reaction was filtered through a celite pad
  3. customthe solvent evaporated to dryness
  4. dry with materialthe organic layer dried over sodium sulphate
  5. customthe solvent removed in vacuo
  6. customAfter purification by flash chromatography
  7. customon silica gel column (DCM/EtOAc/EtOH 6/4/0.5), and further purification by HPLC/MS preparative method 1

Sources & evidence

ORD record
ord-ed8ad42661774de99ce074922af53043
Source dataset
uspto-grants-2015_11
Patent number
US09181258B2

Reaction notes

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