Cesium carbonate → HCID 59558759, compound

HRID 1025018Notes

Reaction equation

HRID 1025018 reaction equation
[CH3:1][C@H:2]1[CH2:7][NH:6][C@H:5]([CH3:8])[CH2:4][N:3]1[S:9]([NH2:12])(=[O:11])=[O:10].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:54]1[CH:59]=[C:58]([O:60][CH3:61])[N:57]=[C:56]([S:62][CH2:63][C:64]2[CH:69]=[CH:68][CH:67]=[C:66]([F:70])[C:65]=2[F:71])[N:55]=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:71][C:65]1[C:66]([F:70])=[CH:67][CH:68]=[CH:69][C:64]=1[CH2:63][S:62][C:56]1[N:55]=[C:54]([NH:12][S:9]([N:3]2[CH2:4][C@@H:5]([CH3:8])[NH:6][CH2:7][C@@H:2]2[CH3:1])(=[O:10])=[O:11])[CH:59]=[C:58]([O:60][CH3:61])[N:57]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 53628415HCID 53628415, compoundHCID 866198774-Chloro-2-([(2,3-difluorophenyl)methyl]thio]-6-methoxypyrimidine

Product 1

HCID 59558759HCID 59558759, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a solution of (2R,5S)-2,5-dimethylpiperazine (2 g) in dioxane (100 ml) was added sulfamide (2.5 g) and the reaction mixture was then heated at reflux in dioxane (100 ml) for 72 h. The reaction mixture was partitioned between EtOAc (150 ml) and H2O (150 ml) and the aqueous re-extracted with EtOAc (2×150 ml). Organics were collected, dried and reduced in vacuo to give (2S,5R)-2,5-dimethylpiperazine-1-sulfonamide as a white solid (1.2 g). A mixture of (2S,5R)-2,5-dimethylpiperazine-1-sulfonamide (0.38 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, 4-Chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-triethoxypyrimidine (the product from example 35 step i), 0.4 g) in dioxane (20 mL) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 4 h. The reaction mixture was then reduced in vacuo and the residue partitioned 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 a yellow solid. This residue was then purified by prep HPLC to give the title compound as a white solid. Yield: 9 mg

Workup

  1. temperaturewas heated
  2. temperature300 W, open vessel with cooling for 4 h
  3. customthe residue partitioned 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)
  7. customto give a yellow solid
  8. customThis residue was then purified by prep HPLC

Sources & evidence

ORD record
ord-ebc3a30fa7d64d18aaeff96b1e33c5f1
Source dataset
uspto-grants-2014_05
Patent number
US08722883B2

Reaction notes

Loading…