Piperazine → HCID 57678298, compound

HRID 491426Notes

Reaction equation

HRID 491426 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11](=[S:21])[NH:12][C:13]2[C:18](Br)=[CH:17][CH:16]=[CH:15][C:14]=2Br)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].CC(C)([O-])C.[Na+].[NH:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[S:21][C:14]3[CH:15]=[CH:16][CH:17]=[C:18]([N:34]4[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]4)[C:13]=3[N:12]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 4837PiperazineHCID 10796Cesium carbonateHCID 23676156Sodium t-butoxideHCID 57678306HCID 57678306, compound

Product 1

HCID 57678298HCID 57678298, compoundYield 42%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

4-tert-butyl-N-(2,6-dibromophenyl)benzenecarbothioamide prepared as in Example 19 (0.200 g, 0.468 mmol) was dissolved in dioxane (4 mL) and treated with Pd2 dba3 (4.3 mg, 0.0468 mmol), o-biphenyl(tBu)2P (15.4 mg, 0.0515 mmol) and Cs2CO3 (0.229 g, 0.702 mmol). The mixture was heated to 80° C. for 2 h until the starting material was consumed and cooled. To the reaction mixture was then added toluene (2 mL), Pd2 dba3 (4.3 mg, 0.0468 mmol), o-biphenyl(tBu)2P (15.4 mg, 0.0515 mmol), sodium tert-butoxide (0.090 g, 0.936 mmol) and piperazine (0.403 g, 4.68 mmol). The mixture was heated at 80° C. for 1 h and filtered through celite. The filtrate was diluted with dichloromethane, washed with water and saturated sodium chloride, and concentrated. The crude material was purified by reverse-phase HPLC to yield 69.5 mg (42%) of the product. MS (ES) m/z 352.1; HPLC Method B, purity 100% at 210-370 nm, 9.8 min.; 99.4% at 310 nm, 9.8 min.; HRMS: calcd for C21H25N3S+H+, 352.18419; found (ESI, [M+H]+), 352.1841.

Workup

  1. customwas consumed
  2. temperaturecooled
  3. temperatureThe mixture was heated at 80° C. for 1 h
  4. filtrationfiltered through celite
  5. additionThe filtrate was diluted with dichloromethane
  6. washwashed with water and saturated sodium chloride
  7. concentrationconcentrated
  8. customThe crude material was purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-a3b4616a84da43a48dcc28980c83da54
Source dataset
uspto-grants-2009_05
Patent number
US07531542B2

Reaction notes

Loading…