Cesium carbonate → Tert-butyl 4-({[2-[(2,3-difluorobenzyl)thio]-6-(3-hydroxypropoxy)pyrimidin-4-yl]amino)sulfonyl}piperazine-1-carboxylate

HRID 2388907Notes

Reaction equation

HRID 2388907 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([S:14]([NH2:17])(=[O:16])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])[CH3:3].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:59]1[N:64]=[C:63]([S:65][CH2:66][C:67]2[CH:72]=[CH:71][CH:70]=[C:69]([F:73])[C:68]=2[F:74])[N:62]=[C:61]([O:75][CH2:76][CH2:77][CH2:78][OH:79])[CH:60]=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]>[F:74][C:68]1[C:69]([F:73])=[CH:70][CH:71]=[CH:72][C:67]=1[CH2:66][S:65][C:63]1[N:64]=[C:59]([NH:17][S:14]([N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:9][CH2:10]2)(=[O:16])=[O:15])[CH:60]=[C:61]([O:75][CH2:76][CH2:77][CH2:78][OH:79])[N:62]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 53628347tert-Butyl 4-sulfamoylpiperazine-1-carboxylateHCID 866198943-({6-Chloro-2-[(2,3-difluorobenzyl)thio]pyrimidin-4-yl}oxy)propan-1-ol2×

Product 1

HCID 67051278Tert-butyl 4-({[2-[(2,3-difluorobenzyl)thio]-6-(3-hydroxypropoxy)pyrimidin-4-yl]amino)sulfonyl}piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-(aminosulfonyl)-1-piperazinecarboxylic acid-1,1-dimethylethyl ester (the product from example 15, step i), 0.4 g), tris(dibenzylideneacetone)dipalladium (0) (50 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (50 mg), cesium carbonate (0.43 g) and 3-({6-chloro-2-[(2,3-difluorobenzyl)thio]pyrimidin-4-yl}oxy)propan-1-ol (the product from step i), 0.4 g) in 1,4-dioxane (40 ml) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 3 h. The reaction mixture was then reduced in vacuo and the residue separated between DCM (150 ml) and H2O (150 ml). The organics were separated and the aqueous layer was re-extracted with DCM (2×150 ml). Organics were combined, dried (MgSO4) and reduced in vacuo to give the subtitle compound as a yellow solid. Yield 0.83 g

Workup

  1. temperaturewas heated
  2. temperature300 W, open vessel with cooling for 3 h
  3. customthe residue separated between DCM (150 ml) and H2O (150 ml)
  4. customThe organics were separated
  5. extractionthe aqueous layer was re-extracted with DCM (2×150 ml)
  6. dry with materialdried (MgSO4)

Sources & evidence

ORD record
ord-3dc080e39ddc4202aa6a4b6667b70baf
Source dataset
uspto-grants-2012_09
Patent number
US08269002B2

Reaction notes

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