Cesium carbonate → HCID 53628372, compound

HRID 1175447Notes

Reaction equation

HRID 1175447 reaction equation
[N:1]1([S:5]([NH2:8])(=[O:7])=[O:6])[CH2:4][CH2:3][CH2:2]1.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:50]1[CH:55]=[C:54]([O:56][C@H:57]([C@H:59]2[CH2:63][O:62][C:61]3([CH2:68][CH2:67][CH2:66][CH2:65][CH2:64]3)[O:60]2)[CH3:58])[N:53]=[C:52]([S:69][CH2:70][C:71]2[CH:76]=[CH:75][CH:74]=[C:73]([F:77])[C:72]=2[F:78])[N:51]=1.[Cl-].[NH4+]>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:78][C:72]1[C:73]([F:77])=[CH:74][CH:75]=[CH:76][C:71]=1[CH2:70][S:69][C:52]1[N:51]=[C:50]([NH:8][S:5]([N:1]2[CH2:4][CH2:3][CH2:2]2)(=[O:7])=[O:6])[CH:55]=[C:54]([O:56][C@H:57]([C@H:59]2[CH2:63][O:62][C:61]3([CH2:68][CH2:67][CH2:66][CH2:65][CH2:64]3)[O:60]2)[CH3:58])[N:53]=1

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 450805661-AzetidinesulfonamideHCID 86619884HCID 86619884, compound2×

Product 1

HCID 53628372HCID 53628372, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of azetidine-1-sulfonamide (prepared according to patent WO 2004/011443, 0.131 g), tris(dibenzylideneacetone)-dipalladium (0) (22 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (11 mg), cesium carbonate (0.117 g) and 4-chloro-2-[(2,3-difluorobenzyl)thio]-6-{(1S)-1-[(2R)-1,4-dioxaspiro[4.5]dec-2-yl]ethoxy}pyrimidine (the product of step i) (0.10 g) in anhydrous dioxane (5 ml) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 15 min. Saturated aqueous ammonium chloride was added and the resulting mixture extracted with EtOAc. The combined organic extracts were washed with saturated aqueous sodium chloride, dried with sodium sulfate, filtered and evaporated. The residue was purified by column chromatography on silica using a 1:19 to 3:7 mixture of EtOAc and iso-hexane as eluent and then by reverse phase HPLC (gradient 25-95% acetonitrile in 0.1% ammonium acetate) to give the subtitle compound as a colourless gum Yield: 43 mg

Workup

  1. temperaturewas heated
  2. temperature300 W, open vessel with cooling for 15 min
  3. extractionthe resulting mixture extracted with EtOAc
  4. washThe combined organic extracts were washed with saturated aqueous sodium chloride
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography on silica using a 1:19
  9. additionto 3:7 mixture of EtOAc and iso-hexane as eluent

Sources & evidence

ORD record
ord-1747379bb1a0493c8fef8dc2c9dbc163
Source dataset
uspto-grants-2010_11
Patent number
US07838675B2

Reaction notes

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