Cesium carbonate → tert-Butyl 4-[({2-[(2,3-difluorobenzyl)thio]-6-methoxypyrimidin-4-yl}amino)sulfonyl]-1,4-diazepane-1-carboxylate

HRID 2388879Notes

Reaction equation

HRID 2388879 reaction equation
[NH2:1][S:2]([N:5]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7][CH2:6]1)(=[O:4])=[O: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:60]1[CH:65]=[C:64]([O:66][CH3:67])[N:63]=[C:62]([S:68][CH2:69][C:70]2[CH:75]=[CH:74][CH:73]=[C:72]([F:76])[C:71]=2[F:77])[N:61]=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:77][C:71]1[C:72]([F:76])=[CH:73][CH:74]=[CH:75][C:70]=1[CH2:69][S:68][C:62]1[N:61]=[C:60]([NH:1][S:2]([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7][CH2:6]2)(=[O:3])=[O:4])[CH:65]=[C:64]([O:66][CH3:67])[N:63]=1

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67051265Tert-butyl 4-sulfamoyl-1,4-diazepane-1-carboxylateHCID 866198774-Chloro-2-([(2,3-difluorophenyl)methyl]thio]-6-methoxypyrimidine2×

Product 1

HCID 53628411tert-Butyl 4-[({2-[(2,3-difluorobenzyl)thio]-6-methoxypyrimidin-4-yl}amino)sulfonyl]-1,4-diazepane-1-carboxylate

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of tert-Butyl 4-(aminosulfonyl)-1,4-diazepane-1-carboxylate (the product of example 75, 0.277 g), tris(dibenzylideneacetone)-dipalladium (0) (45 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (24 mg), cesium carbonate (0.242 g) and 4-chloro-2-([(2,3-difluorophenyl)methyl]thio]-6-methoxypyrimidine (the product of example 35 step i, 0.15 g) in anhydrous dioxane (6 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 to give the subtitle compound as a yellow oil. Yield: 0.223 g

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-6067a76de9064371ad23029884ff1dc5
Source dataset
uspto-grants-2012_09
Patent number
US08269002B2

Reaction notes

Loading…